Matthew B. Frieman, PhD
Alicia and Yaya Viral Pathogen Research Professor of Microbiology & Immunology
- Academic Title: Professor
- Primary Appointment: Microbiology and Immunology
- Email: mfrieman@som.umaryland.edu
- Location: HSF2, 416
- Phone (Primary): 410-706-2539
Education and Training
- Washington University in St Louis, BA, Biology, 1994-1998
- Johns Hopkins University School of Medicine, Baltimore MD, Cellular and Molecular Medicine Graduate Program, Department of Molecular Biology and Genetics, PhD, 1998-2004
- University of North Carolina at Chapel Hill, Post-doctoral fellow in the lab of Dr. Ralph Baric, Department of Epidemiology/Department of Microbiology and Immunology, 2004-2009
Biosketch
My overall research goal is to create therapeutic interventions for viruses of public health concern by developing a detailed understanding of how the viruses interact with the host. My research has focused on the recently emerged and highly pathogenic coronaviruses: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2/COVID19), as well as Influenza virus. The coronaviruses cause severe lung disease, are highly lethal and yet there are no FDA approved therapeutics that target them.
Important to understanding these diseases has been our development, characterization and utilization of mouse models of disease for SARS-CoV, MERS-CoV and SARS-CoV-2. The rapid and successful development of these models has allowed us to unravel the cellular and physiological basis for disease of these viruses. In addition, the creation of these models has allowed for therapeutic development of vaccines, antibodies, small molecules, novel and repurposed drugs and other therapeutics. Critical to my research is the synergy of our in vitro and in vivo models of disease that allow us deep understandings of how these viruses work.
Work in the lab includes the identification of host factors that effect viral replication and the use of novel yeast screening techniques to identify small molecules that inhibit those proteins for use as therapeutics. In addition, we are identifying novel and repurposed drugs, antibodies and vaccines for Influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2 inhibition. Combining our in vitro and in vivo systems identifies key proteins and nodes of regulation for further therapeutic targeting.
Twitter: @mattfrieman
Research/Clinical Keywords
Coronavirus, MERS, SARS, Influenza, Pathogenesis, anti-viral, therapeutics, diabetes, DPP4, lung, COVID19
Highlighted Publications
McGrath ME, Xue Y, Taylor L, Dillen C, Ardanuy J, Gonzalez-Juarbe N, Baracco L, Kim R, Hart R, Assad-Garcia N, Vashee S, Frieman MB. SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression. PLoS Pathog. 2024 May 23;20(5):e1011669. doi: 10.1371/journal.ppat.1011669. PMID: 38781259; PMCID: PMC11152254.
Logue J, Melville VM, Ardanuy J, Frieman MB. CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication in vitro and in vivo. PLoS Pathog. 2023 Dec 20;19(12):e1011870. doi: 10.1371/journal.ppat.1011870. PMID: 38117830; PMCID: PMC10766180.
Johnson RM, Ardanuy J, Hammond H, Logue J, Jackson L, Baracco L, McGrath M, Dillen C, Patel N, Smith G, Frieman M. Diet-induced obesity and diabetes enhance mortality and reduce vaccine efficacy for SARS-CoV-2. J Virol. 2023 Nov 30;97(11):e0133623. doi: 10.1128/jvi.01336-23. Epub 2023 Oct 17. PMID: 37846985; PMCID: PMC10688338.
Ardanuy J, Johnson R, Dillen C, Taylor L, Hammond H, Weston S, Frieman M. Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses. mBio. 2023 Oct 31;14(5):e0158723. doi: 10.1128/mbio.01587-23. Epub 2023 Aug 15. PMID: 37581442; PMCID: PMC10653794.
Logue J, Johnson RM, Patel N, Zhou B, Maciejewski S, Foreman B, Zhou H, Portnoff AD, Tian JH, Rehman A, McGrath ME, Haupt RE, Weston SM, Baracco L, Hammond H, Guebre-Xabier M, Dillen C, Madhangi M, Greene AM, Massare MJ, Glenn GM, Smith G, Frieman MB. Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants. Nat Commun. 2023 Feb 28;14(1):1130. doi: 10.1038/s41467-022-35606-6. PMID: 36854666; PMCID: PMC9972327.
Additional Publications
1: McGrath ME, Xue Y, Taylor L, Dillen C, Ardanuy J, Gonzalez-Juarbe N, Baracco L, Kim R, Hart R, Assad-Garcia N, Vashee S, Frieman MB. SARS-CoV-2 ORF8 modulates lung inflammation and clinical disease progression. PLoS Pathog. 2024 May 23;20(5):e1011669. doi: 10.1371/journal.ppat.1011669. PMID: 38781259; PMCID: PMC11152254.
2: Mühlemann B, Wilks SH, Baracco L, Bekliz M, Carreño JM, Corman VM, Davis- Gardner ME, Dejnirattisai W, Diamond MS, Douek DC, Drosten C, Eckerle I, Edara VV, Ellis M, Fouchier RAM, Frieman M, Godbole S, Haagmans B, Halfmann PJ, Henry AR, Jones TC, Katzelnick LC, Kawaoka Y, Kimpel J, Krammer F, Lai L, Liu C, Lusvarghi S, Meyer B, Mongkolsapaya J, Montefiori DC, Mykytyn A, Netzl A, Pollett S, Rössler A, Screaton GR, Shen X, Sigal A, Simon V, Subramanian R, Supasa P, Suthar MS, Türeli S, Wang W, Weiss CD, Smith DJ. Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays. Sci Transl Med. 2024 May 15;16(747):eadl1722. doi: 10.1126/scitranslmed.adl1722. Epub 2024 May 15. PMID: 38748773.
3: Wang B, Shen WB, Townsel C, Baracco L, Logue J, Reece EA, Frieman MB, Yang P. Placental SARS-CoV-2 Infection and Its Implications for Increased Risk of Adverse Pregnancy Outcomes. Am J Perinatol. 2024 Jun 10. doi: 10.1055/a-2323-0854. Epub ahead of print. PMID: 38729183.
4: Decker S, Xiao S, Dillen C, Schumacher CM, Milstone AM, Frieman M, Debes AK. Association of Nirmatrelvir/Ritonavir Treatment and COVID-19-Neutralizing Antibody Titers in a Longitudinal Health Care Worker Cohort. Open Forum Infect Dis. 2024 Feb 13;11(2):ofad625. doi: 10.1093/ofid/ofad625. PMID: 38352152; PMCID: PMC10863641.
5: Logue J, Melville VM, Ardanuy J, Frieman MB. CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication in vitro and in vivo. PLoS Pathog. 2023 Dec 20;19(12):e1011870. doi: 10.1371/journal.ppat.1011870. PMID: 38117830; PMCID: PMC10766180.
6: Jassey A, Logue J, Weston S, Wagner MA, Galitska G, Miller K, Frieman M, Jackson WT. SIRT-1 is required for release of enveloped enteroviruses. Elife. 2023 Oct 18;12:RP87993. doi: 10.7554/eLife.87993. PMID: 37850626; PMCID: PMC10584371.
7: Johnson RM, Ardanuy J, Hammond H, Logue J, Jackson L, Baracco L, McGrath M, Dillen C, Patel N, Smith G, Frieman M. Diet-induced obesity and diabetes enhance mortality and reduce vaccine efficacy for SARS-CoV-2. J Virol. 2023 Nov 30;97(11):e0133623. doi: 10.1128/jvi.01336-23. Epub 2023 Oct 17. PMID: 37846985; PMCID: PMC10688338.
8: Mühlemann B, Wilks SH, Baracco L, Bekliz M, Carreño JM, Corman VM, Davis- Gardner ME, Dejnirattisai W, Diamond MS, Douek DC, Drosten C, Eckerle I, Edara VV, Ellis M, Fouchier RAM, Frieman M, Godbole S, Haagmans B, Halfmann PJ, Henry AR, Jones TC, Katzelnick LC, Kawaoka Y, Kimpel J, Krammer F, Lai L, Liu C, Lusvarghi S, Meyer B, Mongkolsapaya J, Montefiori DC, Mykytyn A, Netzl A, Pollett S, Rössler A, Screaton GR, Shen X, Sigal A, Simon V, Subramanian R, Supasa P, Suthar M, Türeli S, Wang W, Weiss CD, Smith DJ. Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera. bioRxiv [Preprint]. 2023 Sep 27:2023.09.27.559689. doi: 10.1101/2023.09.27.559689. PMID: 37808679; PMCID: PMC10557678.
9: Sunshine S, Puschnik AS, Replogle JM, Laurie MT, Liu J, Zha BS, Nuñez JK, Byrum JR, McMorrow AH, Frieman MB, Winkler J, Qiu X, Rosenberg OS, Leonetti MD, Ye CJ, Weissman JS, DeRisi JL, Hein MY. Systematic functional interrogation of SARS-CoV-2 host factors using Perturb-seq. Nat Commun. 2023 Oct 6;14(1):6245. doi: 10.1038/s41467-023-41788-4. PMID: 37803001; PMCID: PMC10558542.
10: O'Meara TR, Nanishi E, McGrath ME, Barman S, Dong D, Dillen C, Menon M, Seo HS, Dhe-Paganon S, Ernst RK, Levy O, Frieman MB, Dowling DJ. Reduced SARS-CoV-2 mRNA vaccine immunogenicity and protection in mice with diet-induced obesity and insulin resistance. J Allergy Clin Immunol. 2023 Nov;152(5):1107-1120.e6. doi: 10.1016/j.jaci.2023.06.031. Epub 2023 Aug 16. PMID: 37595760; PMCID: PMC10841117.
11: Ardanuy J, Johnson R, Dillen C, Taylor L, Hammond H, Weston S, Frieman M. Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses. mBio. 2023 Oct 31;14(5):e0158723. doi: 10.1128/mbio.01587-23. Epub 2023 Aug 15. PMID: 37581442; PMCID: PMC10653794.
12: Li M, Ayyanathan K, Dittmar M, Miller J, Tapescu I, Lee JS, McGrath ME, Xue Y, Vashee S, Schultz DC, Frieman MB, Cherry S. SARS-CoV-2 ORF6 protein does not antagonize interferon signaling in respiratory epithelial Calu-3 cells during infection. mBio. 2023 Aug 31;14(4):e0119423. doi: 10.1128/mbio.01194-23. Epub 2023 Jun 28. PMID: 37377442; PMCID: PMC10470815.
13: Logue J, Melville VM, Ardanuy J, Frieman MB. CNP blocks mitochondrial depolarization and inhibits SARS-CoV-2 replication <i>in vitro</i> and <i>in vivo</i>. bioRxiv [Preprint]. 2023 Dec 19:2023.06.09.544327. doi: 10.1101/2023.06.09.544327. Update in: PLoS Pathog. 2023 Dec 20;19(12):e1011870. doi: 10.1371/journal.ppat.1011870. PMID: 37333151; PMCID: PMC10274905.
14: Rodriguez-Rodriguez BA, Ciabattoni GO, Duerr R, Valero-Jimenez AM, Yeung ST, Crosse KM, Schinlever AR, Bernard-Raichon L, Rodriguez Galvan J, McGrath ME, Vashee S, Xue Y, Loomis CA, Khanna KM, Cadwell K, Desvignes L, Frieman MB, Ortigoza MB, Dittmann M. A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8. Nat Commun. 2023 May 25;14(1):3026. doi: 10.1038/s41467-023-38783-0. PMID: 37230979; PMCID: PMC10211296.
15: Sperry MM, Oskotsky TT, Marić I, Kaushal S, Takeda T, Horvath V, Powers RK, Rodas M, Furlong B, Soong M, Prabhala P, Goyal G, Carlson KE, Wong RJ, Kosti I, Le BL, Logue J, Hammond H, Frieman M, Stevenson DK, Ingber DE, Sirota M, Novak R. Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients. PLoS Comput Biol. 2023 May 5;19(5):e1011050. doi: 10.1371/journal.pcbi.1011050. PMID: 37146076; PMCID: PMC10191356.
16: Nanishi E, Borriello F, Seo HS, O'Meara TR, McGrath ME, Saito Y, Chen J, Diray-Arce J, Song K, Xu AZ, Barman S, Menon M, Dong D, Caradonna TM, Feldman J, Hauser BM, Schmidt AG, Baden LR, Ernst RK, Dillen C, Yu J, Chang A, Hilgers L, Platenburg PP, Dhe-Paganon S, Barouch DH, Ozonoff A, Zanoni I, Frieman MB, Dowling DJ, Levy O. Publisher Correction: Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice. NPJ Vaccines. 2023 Mar 3;8(1):30. doi: 10.1038/s41541-023-00634-w. Erratum for: NPJ Vaccines. 2023 Feb 14;8(1):18. doi: 10.1038/s41541-023-00610-4. PMID: 36869134; PMCID: PMC9982769.
17: Logue J, Johnson RM, Patel N, Zhou B, Maciejewski S, Foreman B, Zhou H, Portnoff AD, Tian JH, Rehman A, McGrath ME, Haupt RE, Weston SM, Baracco L, Hammond H, Guebre-Xabier M, Dillen C, Madhangi M, Greene AM, Massare MJ, Glenn GM, Smith G, Frieman MB. Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants. Nat Commun. 2023 Feb 28;14(1):1130. doi: 10.1038/s41467-022-35606-6. PMID: 36854666; PMCID: PMC9972327.
18: Nanishi E, Borriello F, Seo HS, O'Meara TR, McGrath ME, Saito Y, Chen J, Diray-Arce J, Song K, Xu AZ, Barman S, Menon M, Dong D, Caradonna TM, Feldman J, Hauser BM, Schmidt AG, Baden LR, Ernst RK, Dillen C, Yu J, Chang A, Hilgers L, Platenburg PP, Dhe-Paganon S, Barouch DH, Ozonoff A, Zanoni I, Frieman MB, Dowling DJ, Levy O. Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice. NPJ Vaccines. 2023 Feb 14;8(1):18. doi: 10.1038/s41541-023-00610-4. Erratum in: NPJ Vaccines. 2023 Mar 3;8(1):30. doi: 10.1038/s41541-023-00634-w. PMID: 36788219; PMCID: PMC9927065.
19: Goodrum F, Lowen AC, Lakdawala S, Alwine J, Casadevall A, Imperiale MJ, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A. Virology under the Microscope-a Call for Rational Discourse. mSphere. 2023 Apr 20;8(2):e0003423. doi: 10.1128/msphere.00034-23. Epub 2023 Jan 26. PMID: 36700653; PMCID: PMC10117089.
20: Goodrum F, Lowen AC, Lakdawala S, Alwine J, Casadevall A, Imperiale MJ, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A. Virology under the Microscope-a Call for Rational Discourse. mBio. 2023 Feb 28;14(1):e0018823. doi: 10.1128/mbio.00188-23. Epub 2023 Jan 26. PMID: 36700642; PMCID: PMC9973315.
21: Goodrum F, Lowen AC, Lakdawala S, Alwine J, Casadevall A, Imperiale MJ, Atwood W, Avgousti D, Baines J, Banfield B, Banks L, Bhaduri-McIntosh S, Bhattacharya D, Blanco-Melo D, Bloom D, Boon A, Boulant S, Brandt C, Broadbent A, Brooke C, Cameron C, Campos S, Caposio P, Chan G, Cliffe A, Coffin J, Collins K, Damania B, Daugherty M, Debbink K, DeCaprio J, Dermody T, Dikeakos J, DiMaio D, Dinglasan R, Duprex WP, Dutch R, Elde N, Emerman M, Enquist L, Fane B, Fernandez-Sesma A, Flenniken M, Frappier L, Frieman M, Frueh K, Gack M, Gaglia M, Gallagher T, Galloway D, García-Sastre A, Geballe A, Glaunsinger B, Goff S, Greninger A, Hancock M, Harris E, Heaton N, Heise M, Heldwein E, Hogue B, Horner S, Hutchinson E, Hyser J, Jackson W, Kalejta R, Kamil J, Karst S, Kirchhoff F, Knipe D, Kowalik T, Lagunoff M, Laimins L, Langlois R, Lauring A, Lee B, Leib D, Liu SL, Longnecker R, Lopez C, Luftig M, Lund J, Manicassamy B, McFadden G, McIntosh M, Mehle A, Miller WA, Mohr I, Moody C, Moorman N, Moscona A, Mounce B, Munger J, Münger K, Murphy E, Naghavi M, Nelson J, Neufeldt C, Nikolich J, O'Connor C, Ono A, Orenstein W, Ornelles D, Ou JH, Parker J, Parrish C, Pekosz A, Pellett P, Pfeiffer J, Plemper R, Polyak S, Purdy J, Pyeon D, Quinones-Mateu M, Renne R, Rice C, Schoggins J, Roller R, Russell C, Sandri-Goldin R, Sapp M, Schang L, Schmid S, Schultz-Cherry S, Semler B, Shenk T, Silvestri G, Simon V, Smith G, Smith J, Spindler K, Stanifer M, Subbarao K, Sundquist W, Suthar M, Sutton T, Tai A, Tarakanova V, tenOever B, Tibbetts S, Tompkins S, Toth Z, van Doorslaer K, Vignuzzi M, Wallace N, Walsh D, Weekes M, Weinberg J, Weitzman M, Weller S, Whelan S, White E, Williams B, Wobus C, Wong S, Yurochko A. Virology under the Microscope-a Call for Rational Discourse. J Virol. 2023 Feb 28;97(2):e0008923. doi: 10.1128/jvi.00089-23. Epub 2023 Jan 26. PMID: 36700640; PMCID: PMC9972907.
22: Rao X, Razavi M, Mihai G, Wei Y, Braunstein Z, Frieman MB, Sun XJ, Gong Q, Chen J, Zhao G, Liu Z, Quon MJ, Dong L, Rajagopalan S, Zhong J. Dipeptidyl Peptidase 4/Midline-1 Axis Promotes T Lymphocyte Motility in Atherosclerosis. Adv Sci (Weinh). 2023 Mar;10(9):e2204194. doi: 10.1002/advs.202204194. Epub 2023 Jan 22. PMID: 36683148; PMCID: PMC10037965.
23: Haupt R, Baracco L, Harberts EM, Loganathan M, Kerstetter LJ, Krammer F, Coughlan L, Ernst RK, Frieman MB. Enhancing the protection of influenza virus vaccines with BECC TLR4 adjuvant in aged mice. Sci Rep. 2023 Jan 13;13(1):715. doi: 10.1038/s41598-023-27965-x. PMID: 36639569; PMCID: PMC9838488.
24: Brook B, Fatou B, Kumar Checkervarty A, Barman S, Sweitzer C, Bosco AN, Sherman AC, Baden LR, Morrocchi E, Sanchez-Schmitz G, Palma P, Nanishi E, O'Meara TR, McGrath ME, Frieman MB, Soni D, van Haren SD, Ozonoff A, Diray-Arce J, Steen H, Dowling DJ, Levy O. The mRNA vaccine BNT162b2 demonstrates impaired T<sub>H</sub>1 immunogenicity in human elders <i>in vitro</i> and aged mice <i>in vivo</i>. Res Sq [Preprint]. 2022 Dec 21:rs.3.rs-2395118. doi: 10.21203/rs.3.rs-2395118/v1. PMID: 36597547; PMCID: PMC9810224.
25: O'Meara TR, Nanishi E, McGrath ME, Barman S, Dong D, Dillen C, Menon M, Seo HS, Dhe-Paganon S, Ernst RK, Levy O, Frieman MB, Dowling DJ. Reduced SARS-CoV-2 mRNA vaccine immunogenicity and protection in mice with diet-induced obesity and insulin resistance. bioRxiv [Preprint]. 2022 Dec 7:2022.12.07.519460. doi: 10.1101/2022.12.07.519460. Update in: J Allergy Clin Immunol. 2023 Nov;152(5):1107-1120.e6. doi: 10.1016/j.jaci.2023.06.031. PMID: 36523401; PMCID: PMC9753785.
26: Sajadi MM, Myers A, Logue J, Saadat S, Shokatpour N, Quinn J, Newman M, Deming M, Rikhtegaran Tehrani Z, Magder LS, Karimi M, Abbasi A, Shlyak M, Baracco L, Frieman MB, Crotty S, Harris AD. Mucosal and Systemic Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination Determined by Severity of Primary Infection. mSphere. 2022 Dec 21;7(6):e0027922. doi: 10.1128/msphere.00279-22. Epub 2022 Nov 2. PMID: 36321826; PMCID: PMC9769618.
27: Johnson R, Ardunay J, Hammond H, Logue J, Jackson L, Baracco L, McGrath M, Dillen C, Patel N, Smith G, Frieman M. Diet Induced Obesity and Diabetes Enhance Mortality and Reduces Vaccine Efficacy for SARS-CoV-2. bioRxiv [Preprint]. 2023 May 5:2022.10.15.512291. doi: 10.1101/2022.10.15.512291. Update in: J Virol. 2023 Nov 30;97(11):e0133623. doi: 10.1128/jvi.01336-23. PMID: 36299426; PMCID: PMC9603822.
28: Lai J, Coleman KK, Tai SHS, German J, Hong F, Albert B, Esparza Y, Srikakulapu AK, Schanz M, Maldonado IS, Oertel M, Fadul N, Gold TL, Weston S, Mullins K, McPhaul KM, Frieman M, Milton DK. Exhaled Breath Aerosol Shedding of Highly Transmissible Versus Prior Severe Acute Respiratory Syndrome Coronavirus 2 Variants. Clin Infect Dis. 2023 Mar 4;76(5):786-794. doi: 10.1093/cid/ciac846. PMID: 36285523; PMCID: PMC9620356.
29: Rodriguez-Rodriguez BA, Ciabattoni GO, Duerr R, Valero-Jimenez AM, Yeung ST, Crosse KM, Schinlever AR, Bernard-Raichon L, Rodriguez-Galvan JJ, McGrath ME, Vashee S, Xue Y, Loomis C, Khanna KM, Cadwell K, Desvignes L, Frieman MF, Ortigoza MB, Dittmann M. A neonatal mouse model characterizes transmissibility of SARS-CoV-2 variants and reveals a role for ORF8. bioRxiv [Preprint]. 2023 Mar 24:2022.10.04.510658. doi: 10.1101/2022.10.04.510658. Update in: Nat Commun. 2023 May 25;14(1):3026. doi: 10.1038/s41467-023-38783-0. PMID: 36238716; PMCID: PMC9558433.
30: Jha A, Barker D, Lew J, Manoharan V, van Kessel J, Haupt R, Toth D, Frieman M, Falzarano D, Kodihalli S. Efficacy of COVID-HIGIV in animal models of SARS- CoV-2 infection. Sci Rep. 2022 Oct 10;12(1):16956. doi: 10.1038/s41598-022-21223-2. PMID: 36216961; PMCID: PMC9549041.
31: Ji Y, Zhang Q, Cheng L, Ge J, Wang R, Fang M, Mucker EM, Chen P, Ma J, Zhang R, Li C, Hammond H, Baracco L, Holbrook M, Frieman M, Zhang Z, Wang X, Hooper JW, Zhang L, Zhu Q. Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2. Front Immunol. 2022 Sep 14;13:980435. doi: 10.3389/fimmu.2022.980435. PMID: 36189212; PMCID: PMC9518701.
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71: Guebre-Xabier M, Patel N, Tian JH, Zhou B, Maciejewski S, Lam K, Portnoff AD, Massare MJ, Frieman MB, Piedra PA, Ellingsworth L, Glenn G, Smith G. NVX- CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge. Vaccine. 2020 Nov 25;38(50):7892-7896. doi: 10.1016/j.vaccine.2020.10.064. Epub 2020 Oct 23. PMID: 33139139; PMCID: PMC7584426.
72: Gordon DE, Hiatt J, Bouhaddou M, Rezelj VV, Ulferts S, Braberg H, Jureka AS, Obernier K, Guo JZ, Batra J, Kaake RM, Weckstein AR, Owens TW, Gupta M, Pourmal S, Titus EW, Cakir M, Soucheray M, McGregor M, Cakir Z, Jang G, O'Meara MJ, Tummino TA, Zhang Z, Foussard H, Rojc A, Zhou Y, Kuchenov D, Hüttenhain R, Xu J, Eckhardt M, Swaney DL, Fabius JM, Ummadi M, Tutuncuoglu B, Rathore U, Modak M, Haas P, Haas KM, Naing ZZC, Pulido EH, Shi Y, Barrio-Hernandez I, Memon D, Petsalaki E, Dunham A, Marrero MC, Burke D, Koh C, Vallet T, Silvas JA, Azumaya CM, Billesbølle C, Brilot AF, Campbell MG, Diallo A, Dickinson MS, Diwanji D, Herrera N, Hoppe N, Kratochvil HT, Liu Y, Merz GE, Moritz M, Nguyen HC, Nowotny C, Puchades C, Rizo AN, Schulze-Gahmen U, Smith AM, Sun M, Young ID, Zhao J, Asarnow D, Biel J, Bowen A, Braxton JR, Chen J, Chio CM, Chio US, Deshpande I, Doan L, Faust B, Flores S, Jin M, Kim K, Lam VL, Li F, Li J, Li YL, Li Y, Liu X, Lo M, Lopez KE, Melo AA, Moss FR 3rd, Nguyen P, Paulino J, Pawar KI, Peters JK, Pospiech TH Jr, Safari M, Sangwan S, Schaefer K, Thomas PV, Thwin AC, Trenker R, Tse E, Tsui TKM, Wang F, Whitis N, Yu Z, Zhang K, Zhang Y, Zhou F, Saltzberg D; QCRG Structural Biology Consortium; Hodder AJ, Shun-Shion AS, Williams DM, White KM, Rosales R, Kehrer T, Miorin L, Moreno E, Patel AH, Rihn S, Khalid MM, Vallejo-Gracia A, Fozouni P, Simoneau CR, Roth TL, Wu D, Karim MA, Ghoussaini M, Dunham I, Berardi F, Weigang S, Chazal M, Park J, Logue J, McGrath M, Weston S, Haupt R, Hastie CJ, Elliott M, Brown F, Burness KA, Reid E, Dorward M, Johnson C, Wilkinson SG, Geyer A, Giesel DM, Baillie C, Raggett S, Leech H, Toth R, Goodman N, Keough KC, Lind AL; Zoonomia Consortium; Klesh RJ, Hemphill KR, Carlson-Stevermer J, Oki J, Holden K, Maures T, Pollard KS, Sali A, Agard DA, Cheng Y, Fraser JS, Frost A, Jura N, Kortemme T, Manglik A, Southworth DR, Stroud RM, Alessi DR, Davies P, Frieman MB, Ideker T, Abate C, Jouvenet N, Kochs G, Shoichet B, Ott M, Palmarini M, Shokat KM, García-Sastre A, Rassen JA, Grosse R, Rosenberg OS, Verba KA, Basler CF, Vignuzzi M, Peden AA, Beltrao P, Krogan NJ. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science. 2020 Dec 4;370(6521):eabe9403. doi: 10.1126/science.abe9403. Epub 2020 Oct 15. PMID: 33060197; PMCID: PMC7808408.
73: Martin-Sancho L, Lewinski MK, Pache L, Stoneham CA, Yin X, Pratt D, Churas C, Rosenthal SB, Liu S, De Jesus PD, O'Neill AM, Gounder AP, Nguyen C, Pu Y, Oom AL, Miorin L, Rodriguez-Frandsen A, Urbanowski M, Shaw ML, Chang MW, Benner C, Frieman MB, García-Sastre A, Ideker T, Hultquist JF, Guatelli J, Chanda SK. Functional Landscape of SARS-CoV-2 Cellular Restriction. bioRxiv [Preprint]. 2020 Sep 30:2020.09.29.319566. doi: 10.1101/2020.09.29.319566. Update in: Mol Cell. 2021 Jun 17;81(12):2656-2668.e8. doi: 10.1016/j.molcel.2021.04.008. PMID: 33024967; PMCID: PMC7536870.
74: Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX, Albrecht RA, Andersen H, Baric RS, Carroll MW, Cavaleri M, Qin C, Crozier I, Dallmeier K, de Waal L, de Wit E, Delang L, Dohm E, Duprex WP, Falzarano D, Finch CL, Frieman MB, Graham BS, Gralinski LE, Guilfoyle K, Haagmans BL, Hamilton GA, Hartman AL, Herfst S, Kaptein SJF, Klimstra WB, Knezevic I, Krause PR, Kuhn JH, Le Grand R, Lewis MG, Liu WC, Maisonnasse P, McElroy AK, Munster V, Oreshkova N, Rasmussen AL, Rocha-Pereira J, Rockx B, Rodríguez E, Rogers TF, Salguero FJ, Schotsaert M, Stittelaar KJ, Thibaut HJ, Tseng CT, Vergara-Alert J, Beer M, Brasel T, Chan JFW, García-Sastre A, Neyts J, Perlman S, Reed DS, Richt JA, Roy CJ, Segalés J, Vasan SS, Henao-Restrepo AM, Barouch DH. Animal models for COVID-19. Nature. 2020 Oct;586(7830):509-515. doi: 10.1038/s41586-020-2787-6. Epub 2020 Sep 23. PMID: 32967005; PMCID: PMC8136862.
75: Miller K, McGrath ME, Hu Z, Ariannejad S, Weston S, Frieman M, Jackson WT. Coronavirus interactions with the cellular autophagy machinery. Autophagy. 2020 Dec;16(12):2131-2139. doi: 10.1080/15548627.2020.1817280. Epub 2020 Sep 23. PMID: 32964796; PMCID: PMC7755319.
76: Boras B, Jones RM, Anson BJ, Arenson D, Aschenbrenner L, Bakowski MA, Beutler N, Binder J, Chen E, Eng H, Hammond H, Hammond J, Haupt RE, Hoffman R, Kadar EP, Kania R, Kimoto E, Kirkpatrick MG, Lanyon L, Lendy EK, Lillis JR, Logue J, Luthra SA, Ma C, Mason SW, McGrath ME, Noell S, Obach RS, O'Brien MN, O'Connor R, Ogilvie K, Owen D, Pettersson M, Reese MR, Rogers TF, Rossulek MI, Sathish JG, Shirai N, Steppan C, Ticehurst M, Updyke LW, Weston S, Zhu Y, Wang J, Chatterjee AK, Mesecar AD, Frieman MB, Anderson AS, Allerton C. Discovery of a Novel Inhibitor of Coronavirus 3CL Protease for the Potential Treatment of COVID-19. bioRxiv [Preprint]. 2021 Feb 12:2020.09.12.293498. doi: 10.1101/2020.09.12.293498. Update in: Nat Commun. 2021 Oct 18;12(1):6055. doi: 10.1038/s41467-021-26239-2. PMID: 32935104; PMCID: PMC7491518.
77: Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H, Smith G, Patel N, Frieman MB, Haupt RE, Logue J, McGrath M, Weston S, Piedra PA, Desai C, Callahan K, Lewis M, Price-Abbott P, Formica N, Shinde V, Fries L, Lickliter JD, Griffin P, Wilkinson B, Glenn GM. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020 Dec 10;383(24):2320-2332. doi: 10.1056/NEJMoa2026920. Epub 2020 Sep 2. PMID: 32877576; PMCID: PMC7494251.
78: Weston S, Frieman M. Using Yeast to Identify Coronavirus-Host Protein Interactions. Methods Mol Biol. 2020;2203:205-221. doi: 10.1007/978-1-0716-0900-2_15. PMID: 32833214.
79: Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, Reyes HM, Weiss SR, Frieman MB. Broad Anti-coronavirus Activity of Food and Drug Administration- Approved Drugs against SARS-CoV-2 <i>In Vitro</i> and SARS-CoV <i>In Vivo</i>. J Virol. 2020 Oct 14;94(21):e01218-20. doi: 10.1128/JVI.01218-20. PMID: 32817221; PMCID: PMC7565640.
80: Sheahan TP, Frieman MB. The continued epidemic threat of SARS-CoV-2 and implications for the future of global public health. Curr Opin Virol. 2020 Feb;40:37-40. doi: 10.1016/j.coviro.2020.05.010. Epub 2020 Jun 4. PMID: 32569751; PMCID: PMC7269927.
81: Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, Fulton BO, Yan Y, Koon K, Patel K, Chung KM, Hermann A, Ullman E, Cruz J, Rafique A, Huang T, Fairhurst J, Libertiny C, Malbec M, Lee WY, Welsh R, Farr G, Pennington S, Deshpande D, Cheng J, Watty A, Bouffard P, Babb R, Levenkova N, Chen C, Zhang B, Romero Hernandez A, Saotome K, Zhou Y, Franklin M, Sivapalasingam S, Lye DC, Weston S, Logue J, Haupt R, Frieman M, Chen G, Olson W, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science. 2020 Aug 21;369(6506):1010-1014. doi: 10.1126/science.abd0827. Epub 2020 Jun 15. PMID: 32540901; PMCID: PMC7299284.
82: Moitra P, Alafeef M, Dighe K, Frieman MB, Pan D. Selective Naked-Eye Detection of SARS-CoV-2 Mediated by N Gene Targeted Antisense Oligonucleotide Capped Plasmonic Nanoparticles. ACS Nano. 2020 Jun 23;14(6):7617-7627. doi: 10.1021/acsnano.0c03822. Epub 2020 May 28. PMID: 32437124.
83: Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol. 2020 Apr;15(4):247-249. doi: 10.1038/s41565-020-0674-9. PMID: 32203437; PMCID: PMC7094976.
84: Weston S, Frieman MB. COVID-19: Knowns, Unknowns, and Questions. mSphere. 2020 Mar 18;5(2):e00203-20. doi: 10.1128/mSphere.00203-20. PMID: 32188753; PMCID: PMC7082143.
85: Kulcsar KA, Coleman CM, Beck SE, Frieman MB. Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection. JCI Insight. 2019 Oct 17;4(20):e131774. doi: 10.1172/jci.insight.131774. PMID: 31550243; PMCID: PMC6824443.
86: Weston S, Matthews KL, Lent R, Vlk A, Haupt R, Kingsbury T, Frieman MB. A Yeast Suppressor Screen Used To Identify Mammalian SIRT1 as a Proviral Factor for Middle East Respiratory Syndrome Coronavirus Replication. J Virol. 2019 Jul 30;93(16):e00197-19. doi: 10.1128/JVI.00197-19. PMID: 31142674; PMCID: PMC6675885.
87: Banerjee A, Kulcsar K, Misra V, Frieman M, Mossman K. Bats and Coronaviruses. Viruses. 2019 Jan 9;11(1):41. doi: 10.3390/v11010041. PMID: 30634396; PMCID: PMC6356540.
88: Cong Y, Hart BJ, Gross R, Zhou H, Frieman M, Bollinger L, Wada J, Hensley LE, Jahrling PB, Dyall J, Holbrook MR. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells. PLoS One. 2018 Mar 22;13(3):e0194868. doi: 10.1371/journal.pone.0194868. PMID: 29566060; PMCID: PMC5864050.
89: Sisk JM, Frieman MB, Machamer CE. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J Gen Virol. 2018 May;99(5):619-630. doi: 10.1099/jgv.0.001047. Epub 2018 Mar 20. PMID: 29557770; PMCID: PMC6537626.
90: Dyall J, Gross R, Kindrachuk J, Johnson RF, Olinger GG Jr, Hensley LE, Frieman MB, Jahrling PB. Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies. Drugs. 2017 Dec;77(18):1935-1966. doi: 10.1007/s40265-017-0830-1. PMID: 29143192; PMCID: PMC5733787.
91: Rao X, Deiuliis JA, Mihai G, Varghese J, Xia C, Frieman MB, Sztalryd C, Sun XJ, Quon MJ, Taylor SI, Rajagopalan S, Zhong J. Monocyte DPP4 Expression in Human Atherosclerosis Is Associated With Obesity and Dyslipidemia. Diabetes Care. 2018 Jan;41(1):e1-e3. doi: 10.2337/dc17-0672. Epub 2017 Nov 10. PMID: 29127241; PMCID: PMC5741156.
92: Venkataraman T, Coleman CM, Frieman MB. Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection. J Virol. 2017 May 26;91(12):e00182-17. doi: 10.1128/JVI.00182-17. PMID: 28404843; PMCID: PMC5446658.
93: Venkataraman T, Frieman MB. The role of epidermal growth factor receptor (EGFR) signaling in SARS coronavirus-induced pulmonary fibrosis. Antiviral Res. 2017 Jul;143:142-150. doi: 10.1016/j.antiviral.2017.03.022. Epub 2017 Apr 5. PMID: 28390872; PMCID: PMC5507769.
94: Coleman CM, Venkataraman T, Liu YV, Glenn GM, Smith GE, Flyer DC, Frieman MB. MERS-CoV spike nanoparticles protect mice from MERS-CoV infection. Vaccine. 2017 Mar 14;35(12):1586-1589. doi: 10.1016/j.vaccine.2017.02.012. Epub 2017 Feb 23. PMID: 28237499; PMCID: PMC5423355.
95: Moser LA, Ramirez-Carvajal L, Puri V, Pauszek SJ, Matthews K, Dilley KA, Mullan C, McGraw J, Khayat M, Beeri K, Yee A, Dugan V, Heise MT, Frieman MB, Rodriguez LL, Bernard KA, Wentworth DE, Stockwell TB, Shabman RS. A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses. mSystems. 2016 Jun 7;1(3):e00039-15. doi: 10.1128/mSystems.00039-15. PMID: 27822536; PMCID: PMC5069770.
96: Wirblich C, Coleman CM, Kurup D, Abraham TS, Bernbaum JG, Jahrling PB, Hensley LE, Johnson RF, Frieman MB, Schnell MJ. One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus. J Virol. 2017 Jan 3;91(2):e02040-16. doi: 10.1128/JVI.02040-16. PMID: 27807241; PMCID: PMC5215356.
97: Coleman CM, Sisk JM, Halasz G, Zhong J, Beck SE, Matthews KL, Venkataraman T, Rajagopalan S, Kyratsous CA, Frieman MB. CD8+ T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome. J Virol. 2016 Dec 16;91(1):e01825-16. doi: 10.1128/JVI.01825-16. PMID: 27795435; PMCID: PMC5165197.
98: Sisk JM, Frieman MB. Screening of FDA-Approved Drugs for Treatment of Emerging Pathogens. ACS Infect Dis. 2015 Sep 11;1(9):401-2. doi: 10.1021/acsinfecdis.5b00089. Epub 2015 Aug 21. PMID: 27617922.
99: Coleman CM, Sisk JM, Mingo RM, Nelson EA, White JM, Frieman MB. Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion. J Virol. 2016 Sep 12;90(19):8924-33. doi: 10.1128/JVI.01429-16. PMID: 27466418; PMCID: PMC5021412.
100: Luke T, Wu H, Zhao J, Channappanavar R, Coleman CM, Jiao JA, Matsushita H, Liu Y, Postnikova EN, Ork BL, Glenn G, Flyer D, Defang G, Raviprakash K, Kochel T, Wang J, Nie W, Smith G, Hensley LE, Olinger GG, Kuhn JH, Holbrook MR, Johnson RF, Perlman S, Sullivan E, Frieman MB. Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. Sci Transl Med. 2016 Feb 17;8(326):326ra21. doi: 10.1126/scitranslmed.aaf1061. PMID: 26888429.
101: Gralinski LE, Ferris MT, Aylor DL, Whitmore AC, Green R, Frieman MB, Deming D, Menachery VD, Miller DR, Buus RJ, Bell TA, Churchill GA, Threadgill DW, Katze MG, McMillan L, Valdar W, Heise MT, Pardo-Manuel de Villena F, Baric RS. Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross. PLoS Genet. 2015 Oct 9;11(10):e1005504. doi: 10.1371/journal.pgen.1005504. PMID: 26452100; PMCID: PMC4599853.
102: Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T, Sundberg EJ, Frieman MB. Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel Mechanism of Glycosylation Interference. J Virol. 2015 Dec;89(23):11820-33. doi: 10.1128/JVI.02274-15. Epub 2015 Sep 16. PMID: 26378163; PMCID: PMC4645327.
103: Coleman CM, Frieman MB. Growth and Quantification of MERS-CoV Infection. Curr Protoc Microbiol. 2015 May 1;37(1):15E.2.1-9. doi: 10.1002/9780471729259.mc15e02s37. PMID: 26344219; PMCID: PMC4735735.
104: Pascal KE, Coleman CM, Mujica AO, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk JM, Matthews KL, Babb R, Chen G, Lai KM, Huang TT, Olson W, Yancopoulos GD, Stahl N, Frieman MB, Kyratsous CA. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8738-43. doi: 10.1073/pnas.1510830112. Epub 2015 Jun 29. PMID: 26124093; PMCID: PMC4507189.
105: McSweegan E, Weaver SC, Lecuit M, Frieman M, Morrison TE, Hrynkow S. The Global Virus Network: Challenging chikungunya. Antiviral Res. 2015 Aug;120:147-52. doi: 10.1016/j.antiviral.2015.06.003. Epub 2015 Jun 10. PMID: 26071007; PMCID: PMC4843800.
106: Mojica SA, Hovis KM, Frieman MB, Tran B, Hsia RC, Ravel J, Jenkins-Houk C, Wilson KL, Bavoil PM. SINC, a type III secreted protein of Chlamydia psittaci, targets the inner nuclear membrane of infected cells and uninfected neighbors. Mol Biol Cell. 2015 May 15;26(10):1918-34. doi: 10.1091/mbc.E14-11-1530. Epub 2015 Mar 18. PMID: 25788290; PMCID: PMC4436835.
107: Astry B, Venkatesha SH, Laurence A, Christensen-Quick A, Garzino-Demo A, Frieman MB, O'Shea JJ, Moudgil KD. Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ. Clin Immunol. 2015 Apr;157(2):228-38. doi: 10.1016/j.clim.2015.01.011. Epub 2015 Feb 7. PMID: 25660987; PMCID: PMC4410084.
108: Nita-Lazar M, Banerjee A, Feng C, Amin MN, Frieman MB, Chen WH, Cross AS, Wang LX, Vasta GR. Desialylation of airway epithelial cells during influenza virus infection enhances pneumococcal adhesion via galectin binding. Mol Immunol. 2015 May;65(1):1-16. doi: 10.1016/j.molimm.2014.12.010. Epub 2015 Jan 16. PMID: 25597246; PMCID: PMC4344939.
109: Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH, Olinger GG, Hensley LE, Jahrling PB. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015 Feb;59(2):1088-99. doi: 10.1128/AAC.03659-14. Epub 2014 Dec 8. PMID: 25487801; PMCID: PMC4335870.
110: Enjuanes L, Sola I, Frieman MB. Virus Research. Nidoviruses I. Foreword. Virus Res. 2014 Dec 19;194:1-2. doi: 10.1016/j.virusres.2014.11.017. PMID: 25483881; PMCID: PMC7134042.
111: Matthews K, Schäfer A, Pham A, Frieman M. The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity. Virol J. 2014 Dec 7;11:209. doi: 10.1186/s12985-014-0209-9. PMID: 25481026; PMCID: PMC4272517.
112: Coleman CM, Frieman MB. Treating MERS-CoV during an outbreak. Lancet Infect Dis. 2014 Nov;14(11):1030-1031. doi: 10.1016/S1473-3099(14)70939-9. Epub 2014 Sep 29. PMID: 25278219; PMCID: PMC7128167.
113: Li J, Sun W, Subrahmanyam PB, Page C, Younger KM, Tiper IV, Frieman M, Kimball AS, Webb TJ. NKT Cell Responses to B Cell Lymphoma. Med Sci (Basel). 2014 Jun 1;2(2):82-97. doi: 10.3390/medsci2020082. PMID: 24955247; PMCID: PMC4063678.
114: Ladner JT, Beitzel B, Chain PS, Davenport MG, Donaldson EF, Frieman M, Kugelman JR, Kuhn JH, O'Rear J, Sabeti PC, Wentworth DE, Wiley MR, Yu GY; Threat Characterization Consortium; Sozhamannan S, Bradburne C, Palacios G. Standards for sequencing viral genomes in the era of high-throughput sequencing. mBio. 2014 Jun 17;5(3):e01360-14. doi: 10.1128/mBio.01360-14. PMID: 24939889; PMCID: PMC4068259.
115: Frieman M. The art of war: battles between virus and host. Curr Opin Virol. 2014 Jun;6:76-7. doi: 10.1016/j.coviro.2014.05.001. Epub 2014 Jun 2. PMID: 24886699; PMCID: PMC4422063.
116: Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M, Johansen LM, Lear-Rooney CM, Glass PJ, Hensley LE, Frieman MB. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93. doi: 10.1128/AAC.03036-14. Epub 2014 May 19. PMID: 24841273; PMCID: PMC4136000.
117: Adedeji AO, Singh K, Kassim A, Coleman CM, Elliott R, Weiss SR, Frieman MB, Sarafianos SG. Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses. Antimicrob Agents Chemother. 2014 Aug;58(8):4894-8. doi: 10.1128/AAC.02994-14. Epub 2014 May 19. PMID: 24841268; PMCID: PMC4136041.
118: Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Smith GE, Frieman MB. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014 May 30;32(26):3169-3174. doi: 10.1016/j.vaccine.2014.04.016. Epub 2014 Apr 13. PMID: 24736006; PMCID: PMC4058772.
119: Coleman CM, Frieman MB. Coronaviruses: important emerging human pathogens. J Virol. 2014 May;88(10):5209-12. doi: 10.1128/JVI.03488-13. Epub 2014 Mar 5. PMID: 24600003; PMCID: PMC4019136.
120: Matthews KL, Coleman CM, van der Meer Y, Snijder EJ, Frieman MB. The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling. J Gen Virol. 2014 Apr;95(Pt 4):874-882. doi: 10.1099/vir.0.062059-0. Epub 2014 Jan 17. PMID: 24443473; PMCID: PMC3973478.
121: Kim WK, Jain D, Sánchez MD, Koziol-White CJ, Matthews K, Ge MQ, Haczku A, Panettieri RA Jr, Frieman MB, López CB. Deficiency of melanoma differentiation- associated protein 5 results in exacerbated chronic postviral lung inflammation. Am J Respir Crit Care Med. 2014 Feb 15;189(4):437-48. doi: 10.1164/rccm.201307-1338OC. PMID: 24417465; PMCID: PMC3977719.
122: Hart BJ, Dyall J, Postnikova E, Zhou H, Kindrachuk J, Johnson RF, Olinger GG, Frieman MB, Holbrook MR, Jahrling PB, Hensley L. Interferon-β and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J Gen Virol. 2014 Mar;95(Pt 3):571-577. doi: 10.1099/vir.0.061911-0. Epub 2013 Dec 9. PMID: 24323636; PMCID: PMC3929173.
123: Coleman CM, Matthews KL, Goicochea L, Frieman MB. Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J Gen Virol. 2014 Feb;95(Pt 2):408-412. doi: 10.1099/vir.0.060640-0. Epub 2013 Nov 6. PMID: 24197535; PMCID: PMC3917065.
124: Coleman CM, Frieman MB. Emergence of the Middle East respiratory syndrome coronavirus. PLoS Pathog. 2013;9(9):e1003595. doi: 10.1371/journal.ppat.1003595. Epub 2013 Sep 5. PMID: 24039577; PMCID: PMC3764217.
125: Page C, Goicochea L, Matthews K, Zhang Y, Klover P, Holtzman MJ, Hennighausen L, Frieman M. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection. J Virol. 2012 Dec;86(24):13334-49. doi: 10.1128/JVI.01689-12. Epub 2012 Sep 26. PMID: 23015710; PMCID: PMC3503056.
126: Huynh J, Li S, Yount B, Smith A, Sturges L, Olsen JC, Nagel J, Johnson JB, Agnihothram S, Gates JE, Frieman MB, Baric RS, Donaldson EF. Evidence supporting a zoonotic origin of human coronavirus strain NL63. J Virol. 2012 Dec;86(23):12816-25. doi: 10.1128/JVI.00906-12. Epub 2012 Sep 19. PMID: 22993147; PMCID: PMC3497669.
127: Frieman M, Basu D, Matthews K, Taylor J, Jones G, Pickles R, Baric R, Engel DA. Yeast based small molecule screen for inhibitors of SARS-CoV. PLoS One. 2011;6(12):e28479. doi: 10.1371/journal.pone.0028479. Epub 2011 Dec 2. PMID: 22164298; PMCID: PMC3229576.
128: Peng X, Gralinski L, Ferris MT, Frieman MB, Thomas MJ, Proll S, Korth MJ, Tisoncik JR, Heise M, Luo S, Schroth GP, Tumpey TM, Li C, Kawaoka Y, Baric RS, Katze MG. Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection. mBio. 2011 Nov 15;2(6):e00198-11. doi: 10.1128/mBio.00198-11. PMID: 22086488; PMCID: PMC3221602.
129: Frieman M, Yount B, Agnihothram S, Page C, Donaldson E, Roberts A, Vogel L, Woodruff B, Scorpio D, Subbarao K, Baric RS. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J Virol. 2012 Jan;86(2):884-97. doi: 10.1128/JVI.05957-11. Epub 2011 Nov 9. PMID: 22072787; PMCID: PMC3255850.
130: Chen WH, Toapanta FR, Shirey KA, Zhang L, Giannelou A, Page C, Frieman MB, Vogel SN, Cross AS. Potential role for alternatively activated macrophages in the secondary bacterial infection during recovery from influenza. Immunol Lett. 2012 Jan 30;141(2):227-34. doi: 10.1016/j.imlet.2011.10.009. Epub 2011 Oct 20. PMID: 22037624; PMCID: PMC3243824.
131: Peng X, Gralinski L, Armour CD, Ferris MT, Thomas MJ, Proll S, Bradel- Tretheway BG, Korth MJ, Castle JC, Biery MC, Bouzek HK, Haynor DR, Frieman MB, Heise M, Raymond CK, Baric RS, Katze MG. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. mBio. 2010 Oct 26;1(5):e00206-10. doi: 10.1128/mBio.00206-10. PMID: 20978541; PMCID: PMC2962437.
132: Donaldson EF, Haskew AN, Gates JE, Huynh J, Moore CJ, Frieman MB. Metagenomic analysis of the viromes of three North American bat species: viral diversity among different bat species that share a common habitat. J Virol. 2010 Dec;84(24):13004-18. doi: 10.1128/JVI.01255-10. Epub 2010 Oct 6. PMID: 20926577; PMCID: PMC3004358.
133: Zornetzer GA, Frieman MB, Rosenzweig E, Korth MJ, Page C, Baric RS, Katze MG. Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice during severe acute respiratory syndrome coronavirus infection. J Virol. 2010 Nov;84(21):11297-309. doi: 10.1128/JVI.01130-10. Epub 2010 Aug 11. PMID: 20702617; PMCID: PMC2953159.
134: Frieman MB, Chen J, Morrison TE, Whitmore A, Funkhouser W, Ward JM, Lamirande EW, Roberts A, Heise M, Subbarao K, Baric RS. SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism. PLoS Pathog. 2010 Apr 8;6(4):e1000849. doi: 10.1371/journal.ppat.1000849. PMID: 20386712; PMCID: PMC2851658.
135: Rockx B, Donaldson E, Frieman M, Sheahan T, Corti D, Lanzavecchia A, Baric RS. Escape from human monoclonal antibody neutralization affects in vitro and in vivo fitness of severe acute respiratory syndrome coronavirus. J Infect Dis. 2010 Mar 15;201(6):946-55. doi: 10.1086/651022. PMID: 20144042; PMCID: PMC2826557.
136: Freundt EC, Yu L, Goldsmith CS, Welsh S, Cheng A, Yount B, Liu W, Frieman MB, Buchholz UJ, Screaton GR, Lippincott-Schwartz J, Zaki SR, Xu XN, Baric RS, Subbarao K, Lenardo MJ. The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death. J Virol. 2010 Jan;84(2):1097-109. doi: 10.1128/JVI.01662-09. Epub 2009 Nov 4. PMID: 19889773; PMCID: PMC2798367.
137: Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG. Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. J Virol. 2009 Jul;83(14):7062-74. doi: 10.1128/JVI.00127-09. Epub 2009 May 6. Erratum in: J Virol. 2009 Sep;83(17):9022. PMID: 19420084; PMCID: PMC2704758.
138: Frieman M, Ratia K, Johnston RE, Mesecar AD, Baric RS. Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J Virol. 2009 Jul;83(13):6689-705. doi: 10.1128/JVI.02220-08. Epub 2009 Apr 15. PMID: 19369340; PMCID: PMC2698564.
139: Frieman M, Baric R. Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev. 2008 Dec;72(4):672-85, Table of Contents. doi: 10.1128/MMBR.00015-08. PMID: 19052324; PMCID: PMC2593566.
140: Basu D, Walkiewicz MP, Frieman M, Baric RS, Auble DT, Engel DA. Novel influenza virus NS1 antagonists block replication and restore innate immune function. J Virol. 2009 Feb;83(4):1881-91. doi: 10.1128/JVI.01805-08. Epub 2008 Dec 3. PMID: 19052087; PMCID: PMC2643796.
141: Zupancic ML, Frieman M, Smith D, Alvarez RA, Cummings RD, Cormack BP. Glycan microarray analysis of Candida glabrata adhesin ligand specificity. Mol Microbiol. 2008 May;68(3):547-59. doi: 10.1111/j.1365-2958.2008.06184.x. PMID: 18394144.
142: Wathelet MG, Orr M, Frieman MB, Baric RS. Severe acute respiratory syndrome coronavirus evades antiviral signaling: role of nsp1 and rational design of an attenuated strain. J Virol. 2007 Nov;81(21):11620-33. doi: 10.1128/JVI.00702-07. Epub 2007 Aug 22. PMID: 17715225; PMCID: PMC2168762.
143: Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane. J Virol. 2007 Sep;81(18):9812-24. doi: 10.1128/JVI.01012-07. Epub 2007 Jun 27. PMID: 17596301; PMCID: PMC2045396.
144: Frieman M, Heise M, Baric R. SARS coronavirus and innate immunity. Virus Res. 2008 Apr;133(1):101-12. doi: 10.1016/j.virusres.2007.03.015. Epub 2007 Apr 23. PMID: 17451827; PMCID: PMC2292640.
145: Kopecky-Bromberg SA, Martínez-Sobrido L, Frieman M, Baric RA, Palese P. Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists. J Virol. 2007 Jan;81(2):548-57. doi: 10.1128/JVI.01782-06. Epub 2006 Nov 15. PMID: 17108024; PMCID: PMC1797484.
146: Baric RS, Sheahan T, Deming D, Donaldson E, Yount B, Sims AC, Roberts RS, Frieman M, Rockx B. SARS coronavirus vaccine development. Adv Exp Med Biol. 2006;581:553-60. doi: 10.1007/978-0-387-33012-9_101. PMID: 17037597; PMCID: PMC7124095.
147: Frieman MB, Yount B, Sims AC, Deming DJ, Morrison TE, Sparks J, Denison M, Heise M, Baric RS. SARS coronavirus accessory ORFs encode luxury functions. Adv Exp Med Biol. 2006;581:149-52. doi: 10.1007/978-0-387-33012-9_26. PMID: 17037522; PMCID: PMC7123626.
148: Yount B, Roberts RS, Sims AC, Deming D, Frieman MB, Sparks J, Denison MR, Davis N, Baric RS. Severe acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice. J Virol. 2005 Dec;79(23):14909-22. doi: 10.1128/JVI.79.23.14909-14922.2005. PMID: 16282490; PMCID: PMC1287583.
149: Frieman MB, Cormack BP. Multiple sequence signals determine the distribution of glycosylphosphatidylinositol proteins between the plasma membrane and cell wall in Saccharomyces cerevisiae. Microbiology (Reading). 2004 Oct;150(Pt 10):3105-14. doi: 10.1099/mic.0.27420-0. PMID: 15470092.
150: Frieman MB, Cormack BP. The omega-site sequence of glycosylphosphatidylinositol-anchored proteins in Saccharomyces cerevisiae can determine distribution between the membrane and the cell wall. Mol Microbiol. 2003 Nov;50(3):883-96. doi: 10.1046/j.1365-2958.2003.03722.x. PMID: 14617149.
151: Frieman MB, McCaffery JM, Cormack BP. Modular domain structure in the Candida glabrata adhesin Epa1p, a beta1,6 glucan-cross-linked cell wall protein. Mol Microbiol. 2002 Oct;46(2):479-92. doi: 10.1046/j.1365-2958.2002.03166.x. PMID: 12406223.
152: Strichman-Almashanu LZ, Lee RS, Onyango PO, Perlman E, Flam F, Frieman MB, Feinberg AP. A genome-wide screen for normally methylated human CpG islands that can identify novel imprinted genes. Genome Res. 2002 Apr;12(4):543-54. doi: 10.1101/gr.224102. PMID: 11932239; PMCID: PMC187522.
Research Interests
Determinants of Host Response to Coronavirus Pathogenesis
We utilize novel mouse models of SARS-CoV and MERS-CoV to identify the host response to infection while identifying pathways and proteins that regulate the response. In the past we have identified STAT1, EGFR and other wound healing factors that regulate disease severity for SARS-CoV. After the emergence of MERS-CoV in 2012 we rapidly developed a mouse model for the virus and have been identifying the host factors and immune response to MERS-CoV infection. Wildtype mice are not permissive to MERS-CoV infection due to the an amino acid difference in the binding site of the MERS-CoV Spike protein with its cell surface receptor Dipeptidyl Peptidase IV (DPP4). We found that the mouse DPP4 does not bind MERS-CoV Spike but the human DPP4 does. We quickly realized that to study MERS-CoV pathogenesis in mice we would have to create a mouse that expressed human DPP4 instead of mouse DPP4. We rapidly produced and characterized a mouse that had human DPP4 knocked-in to the mouse DPP4 loci, replacing the gene but retaining the mouse DPP4 promoter. This allowed for the correct expression kinetics of the human DPP4 in the mice. We found that MERS-CoV infected these mice, produced significant lung pathology and induced a unique inflammatory response in the mice, different from that of SARS-CoV. Using this model, we have further focused on the effects of diabetic comorbidity on disease severity. The reason for focusing on diabetes is because of the patients that have lethal MERS-CoV infection, the vast majority have preexisting comorbidities, the largest of which is Type 2 diabetes (T2D). We have modeled T2D in our MERS-CoV mouse model by feeding the mice a high fat diet for 12 weeks and find that MERS-CoV infection induces a more severe disease in these mice compared to normal mice. The T2D mice have slower inflammatory cell infiltration, enhanced epithelial cell hyperplasia at sites of infection and a skewed immune response. We are currently investigating the role of the MERS-CoV receptor, DPP4, in the T2D response and how its activity effects the immune response to the virus. One striking difference is that Type 2 alveolar cells are infected immediately after inoculation in the diabetic mice, whereas they take 4 days after inoculation to become infected in normal mice. We believe that the Type 2 alveolar cells are more permissive in the diabetic mice to MERS-CoV due to a difference in accessibility of the virus to the cell surface and of a reduced innate immune response of these cells in diabetic mice. Mucus and surfactant levels are reduced on the surface of the alveoli in diabetic mice, allowing for increased virus deposition deep into the lungs, altering their microenvironment and enhancing infection. The same phenomenon will affect not just MERS-CoV but also other respiratory viruses including Influenza virus, bacterial infections including S. aureus and fungal infections including Aspergillus sp. We believe this model will be critical in the future for determining the role of diabetes and other comorbidities in the host response to MERS-CoV and potentially other pathogens.
In vitro modeling of coronavirus:host interactions
We develop a system to use S. cerevisiaeas a tool to identify host proteins and pathways critical for viral replication. Using my background in yeast genetics (PhD Thesis work at The Johns Hopkins University School of Medicine), we find that certain viral proteins expressed in yeast are able to induce a slow growth phenotype. This phenotype is remarkably useful for identifying suppressors/interactors of the pathways that the viral proteins effect, either directly or through their functional interactions with host proteins. We hypothesize that the function of viral proteins in cells will be conserved from mammalian cells to yeast and that these functions can be easily distinguished when the viral proteins are expressed singly rather than during a viral infection. Using a yeast based expression and suppressor screen platform, we have identified novel functional interactions for MERS-CoV and SARS-CoV proteins, as well as extending our screen to Influenza virus, Norovirus and Rotavirus. We are currently targeting these pathways with novel compounds to inhibit its function leading to increased IFN signaling and protection of cells from viral infection. We have used the same growth phenotype in yeast to identify novel anti-viral compounds for SARS-CoV, Influenza virus, MERS-CoV and Chikungunya virus that have been validated in vitro cell culture systems. Our studies are continuing to identify novel host proteins in mammalian cells via initial functional growth screens in yeast. These findings will be followed by in vivoanalysis using the mouse models developed in my laboratory.
Awards and Affiliations
Professional Society Memberships
- 2006-present: Member of the American Society for Virology
- 2008-present: Member of the American Society of Microbiology
Awards and Honors
- 1994-1997: HHMI Summer Research Fellowship to support research in the lab of Dr. Craig Pikaard (Washington Univ. in St. Louis)
- 1995-1997: HHMI Summer Research Travel Award (Wash Univ. in St. Louis)
- 2007: UNC-CH Post-Doctoral Award for Research Excellence
- 2007: ASV Post-Doctoral Travel Scholarship (UNC-CH)
- 2010, 2012: Teaching Commendation for Host Defenses and Infectious Diseases (UMSOM)
- 2014: Winner, Daily Record, Innovator of the Year; Nominated for University of Maryland Research of the Year
- 2015-19: Teaching Commendation for Host Defenses and Infectious Diseases (UMSOM)
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Experimental MERS Treatments Target Host Cell Receptor