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

Weston SM, Haupt R, Logue J, Matthews KL, Frieman M. FDA approved drugs with broad anti-coronaviral activity inhibit SARS-CoV-2 in vitro. J Virol, 2020 Oct 14;94(21):e01218-20. PubMed PMID: 32817221

Weston S, Baracco L, Keller C, Matthews K, McGrath ME, Logue J, Liang J, Dyall J, Holbrook MR, Hensley LE, Jahrling PB, Yu W, MacKerell AD Jr, Frieman MB. The SKI complex is a broad-spectrum, host-directed antiviral drug target for coronaviruses, influenza, and filoviruses. Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30687-30698.

Schultz D, Johnson RM, Ayyanathan K, Miller J, Whig K, Kamalia B, Dittmar M, Weston S, Hammond HL, Dillen C, Castellana L, Lee JS, Li M, Lee E, Constant S, Ferrer M, Thaiss CA, Frieman MB, Cherry S. Pyrimidine biosynthesis inhibitors synergize with nucleoside analogs to block SARS-CoV-2 infection. bioRxiv. 2021 Jun 24;2021.06.24.449811.

Ha Tian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, Logue J, Portnoff AD, Norton J, Guebre-Xabier M, Zhou B, Jacobson K, Maciejewski S, Khatoon R, Wisniewska M, Moffitt W, Kluepfel-Stahl S, Ekechukwu B, Papin J, Boddapati S, Jason Wong C, Piedra PA, Frieman MB, Massare MJ, Fries L, Bengtsson KL, Stertman L, Ellingsworth L, Glenn G, Smith G. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021 Jan 14;12(1):372. doi: 10.1038/s41467-020-20653-8.PMID: 33446655

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. PubMed PMID: 26124093; PubMed Central PMCID: PMC4507189.

1: White JM, Schiffer JT, Bender Ignacio RA, Xu S, Kainov D, Ianevski A,
Aittokallio T, Frieman M, Olinger GG, Polyak SJ. Drug Combinations as a First
Line of Defense against Coronaviruses and Other Emerging Viruses. mBio. 2021 Dec
21;12(6):e0334721. doi: 10.1128/mbio.03347-21. Epub 2021 Dec 21. PMID: 34933447;
PMCID: PMC8689562.

2: Si L, Bai H, Oh CY, Zhang T, Hong F, Jiang A, Ye Y, Jordan TX, Logue J,
McGrath M, Belgur C, Nurani A, Cao W, Prantil-Baun R, Gygi SP, Powers RK,
Frieman M, tenOever BR, Ingber DE. Self-assembling short immunostimulatory
duplex RNAs with broad spectrum antiviral activity. bioRxiv [Preprint]. 2021 Nov
22:2021.11.19.469183. doi: 10.1101/2021.11.19.469183. PMID: 34845453; PMCID:
PMC8629196.

3: Nanishi E, Borriello F, O'Meara TR, McGrath ME, Saito Y, Haupt RE, Seo HS,
van Haren SD, Cavazzoni CB, Brook B, Barman S, Chen J, Diray-Arce J, Doss-Gollin
S, De Leon M, Prevost-Reilly A, Chew K, Menon M, Song K, Xu AZ, Caradonna TM,
Feldman J, Hauser BM, Schmidt AG, Sherman AC, Baden LR, Ernst RK, Dillen C,
Weston SM, Johnson RM, Hammond HL, Mayer R, Burke A, Bottazzi ME, Hotez PJ,
Strych U, Chang A, Yu J, Sage PT, Barouch DH, Dhe-Paganon S, Zanoni I, Ozonoff
A, Frieman MB, Levy O, Dowling DJ. An aluminum hydroxide:CpG adjuvant enhances
protection elicited by a SARS-CoV-2 receptor-binding domain vaccine in aged
mice. Sci Transl Med. 2021 Nov 16:eabj5305. Epub ahead of print. PMID: 34783582.

4: 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, Rosales R, Rossulek MI,
Sathish JG, Shirai N, Steppan C, Ticehurst M, Updyke LW, Weston S, Zhu Y, White
KM, García-Sastre A, Wang J, Chatterjee AK, Mesecar AD, Frieman MB, Anderson AS,
Allerton C. Preclinical characterization of an intravenous coronavirus 3CL
protease inhibitor for the potential treatment of COVID19. Nat Commun. 2021 Oct
18;12(1):6055. doi: 10.1038/s41467-021-26239-2. PMID: 34663813; PMCID:
PMC8523698.

5: Dong J, Zost SJ, Greaney AJ, Starr TN, Dingens AS, Chen EC, Chen RE, Case JB,
Sutton RE, Gilchuk P, Rodriguez J, Armstrong E, Gainza C, Nargi RS, Binshtein E,
Xie X, Zhang X, Shi PY, Logue J, Weston S, McGrath ME, Frieman MB, Brady T,
Tuffy KM, Bright H, Loo YM, McTamney PM, Esser MT, Carnahan RH, Diamond MS,
Bloom JD, Crowe JE Jr. Genetic and structural basis for SARS-CoV-2 variant
neutralization by a two-antibody cocktail. Nat Microbiol. 2021
Oct;6(10):1233-1244. doi: 10.1038/s41564-021-00972-2. Epub 2021 Sep 21. PMID:
34548634; PMCID: PMC8543371.

6: Xiao J, de Mesquita JB, Leung NHL, Adenaiye O, Tai S, Frieman MB, Hong F, Chu
DKW, Ip DKM, Cowling BJ, Milton DK; Prometheus-UMD Consortium. Viral RNA and
infectious influenza virus on mobile phones of influenza patients in Hong Kong
and the United States. J Infect Dis. 2021 Sep 17:jiab464. doi:
10.1093/infdis/jiab464. Epub ahead of print. PMID: 34534320.

7: Adenaiye OO, Lai J, de Mesquita PJB, Hong F, Youssefi S, German J, Tai SS,
Albert B, Schanz M, Weston S, Hang J, Fung C, Chung HK, Coleman KK, Sapoval N,
Treangen T, Berry IM, Mullins K, Frieman M, Ma T, Milton DK; University of
Maryland StopCOVID Research Group. Infectious SARS-CoV-2 in Exhaled Aerosols and
Efficacy of Masks During Early Mild Infection. Clin Infect Dis. 2021 Sep
14:ciab797. doi: 10.1093/cid/ciab797. Epub ahead of print. PMID: 34519774;
PMCID: PMC8522431.

8: Gorman MJ, Patel N, Guebre-Xabier M, Zhu AL, Atyeo C, Pullen KM, Loos C,
Goez-Gazi Y, Carrion R Jr, Tian JH, Yuan D, Bowman KA, Zhou B, Maciejewski S,
McGrath ME, Logue J, Frieman MB, Montefiori D, Mann C, Schendel S, Amanat F,
Krammer F, Saphire EO, Lauffenburger DA, Greene AM, Portnoff AD, Massare MJ,
Ellingsworth L, Glenn G, Smith G, Alter G. Fab and Fc contribute to maximal
protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with
Matrix-M vaccination. Cell Rep Med. 2021 Sep 21;2(9):100405. doi:
10.1016/j.xcrm.2021.100405. Epub 2021 Aug 31. PMID: 34485950; PMCID: PMC8405506.

9: Haupt RE, Harberts EM, Kitz RJ, Strohmeier S, Krammer F, Ernst RK, Frieman
MB. Novel TLR4 adjuvant elicits protection against homologous and heterologous
Influenza A infection. Vaccine. 2021 Aug 23;39(36):5205-5213. doi:
10.1016/j.vaccine.2021.06.085. Epub 2021 Aug 3. PMID: 34362603; PMCID:
PMC8744187.

10: Schultz DC, Johnson RM, Ayyanathan K, Miller J, Whig K, Kamalia B, Dittmar
M, Weston S, Hammond HL, Dillen C, Castellana L, Lee JS, Li M, Lee E, Constant
S, Ferrer M, Thaiss CA, Frieman MB, Cherry S. Pyrimidine biosynthesis inhibitors
synergize with nucleoside analogs to block SARS-CoV-2 infection. bioRxiv
[Preprint]. 2021 Jun 24:2021.06.24.449811. doi: 10.1101/2021.06.24.449811. PMID:
34189531; PMCID: PMC8240684.

11: Frieman M, Harris AD, Herati RS, Krammer F, Mantovani A, Rescigno M, Sajadi
MM, Simon V. SARS-CoV-2 vaccines for all but a single dose for COVID-19
survivors. EBioMedicine. 2021 Jun;68:103401. doi: 10.1016/j.ebiom.2021.103401.
Epub 2021 May 26. PMID: 34051441; PMCID: PMC8149267.

12: Nanishi E, Borriello F, O'Meara TR, McGrath ME, Saito Y, Haupt RE, Seo HS,
van Haren SD, Brook B, Chen J, Diray-Arce J, Doss-Gollin S, Leon M, Chew K,
Menon M, Song K, Xu AZ, Caradonna TM, Feldman J, Hauser BM, Schmidt AG, Sherman
AC, Baden LR, Ernst RK, Dillen C, Weston SM, Johnson RM, Hammond HL, Mayer R,
Burke A, Bottazzi ME, Hotez PJ, Strych U, Chang A, Yu J, Barouch DH, Dhe-Paganon
S, Zanoni I, Ozonoff A, Frieman MB, Levy O, Dowling DJ. Alum:CpG adjuvant
enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic
activation of human elder type 1 immunity. bioRxiv [Preprint]. 2021 May
21:2021.05.20.444848. doi: 10.1101/2021.05.20.444848. PMID: 34031655; PMCID:
PMC8142652.

13: McDonald JT, Enguita FJ, Taylor D, Griffin RJ, Priebe W, Emmett MR, McGrath
M, Sajadi MM, Harris AD, Clement J, Dybas JM, Aykin-Burns N, Guarnieri JW, Singh
LN, Grabham P, Baylin SB, Yousey A, Pearson AN, Corry PM, Saravia-Butler A,
Aunins TR, Nagpal P, Meydan C, Foox J, Mozsary C, Cerqueira B, Zaksas V, Singh
U, Wurtele ES, Costes SV, Galeano D, Paccanaro A, Meinig SL, Hagan RS, Bowman
NM; UNC COVID-19 Pathobiology Consortium, Wolfgang MC, Altinok S, Sapoval N,
Treangen TJ, Frieman M, Vanderburg C, Wallace DC, Schisler J, Mason CE,
Chatterjee A, Meller R, Beheshti A. The Great Deceiver: miR-2392's Hidden Role
in Driving SARS-CoV-2 Infection. bioRxiv [Preprint]. 2021 Apr
27:2021.04.23.441024. doi: 10.1101/2021.04.23.441024. PMID: 33948587; PMCID:
PMC8095194.

14: Si L, Bai H, Rodas M, Cao W, Oh CY, Jiang A, Moller R, Hoagland D, Oishi K,
Horiuchi S, Uhl S, Blanco-Melo D, Albrecht RA, Liu WC, Jordan T, Nilsson-Payant
BE, Golynker I, Frere J, Logue J, Haupt R, McGrath M, Weston S, Zhang T, Plebani
R, Soong M, Nurani A, Kim SM, Zhu DY, Benam KH, Goyal G, Gilpin SE, Prantil-Baun
R, Gygi SP, Powers RK, Carlson KE, Frieman M, tenOever BR, Ingber DE. A human-
airway-on-a-chip for the rapid identification of candidate antiviral
therapeutics and prophylactics. Nat Biomed Eng. 2021 Aug;5(8):815-829. doi:
10.1038/s41551-021-00718-9. Epub 2021 May 3. PMID: 33941899; PMCID: PMC8387338.

15: Martin-Sancho L, Lewinski MK, Pache L, Stoneham CA, Yin X, Becker ME, Pratt
D, Churas C, Rosenthal SB, Liu S, Weston S, De Jesus PD, O'Neill AM, Gounder AP,
Nguyen C, Pu Y, Curry HM, Oom AL, Miorin L, Rodriguez-Frandsen A, Zheng F, Wu C,
Xiong Y, Urbanowski M, Shaw ML, Chang MW, Benner C, Hope TJ, Frieman MB, García-
Sastre A, Ideker T, Hultquist JF, Guatelli J, Chanda SK. Functional landscape of
SARS-CoV-2 cellular restriction. Mol Cell. 2021 Jun 17;81(12):2656-2668.e8. doi:
10.1016/j.molcel.2021.04.008. Epub 2021 Apr 13. PMID: 33930332; PMCID:
PMC8043580.

16: Puhl AC, Fritch EJ, Lane TR, Tse LV, Yount BL, Sacramento CQ, Fintelman-
Rodrigues N, Tavella TA, Maranhão Costa FT, Weston S, Logue J, Frieman M,
Premkumar L, Pearce KH, Hurst BL, Andrade CH, Levi JA, Johnson NJ, Kisthardt SC,
Scholle F, Souza TML, Moorman NJ, Baric RS, Madrid PB, Ekins S. Repurposing the
Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine, and Pyronaridine: In
Vitro Activity against SARS-CoV-2 and Potential Mechanisms. ACS Omega. 2021
Mar 10;6(11):7454-7468. doi: 10.1021/acsomega.0c05996. PMID: 33778258; PMCID:
PMC7992063.

17: Dong J, Zost S, Greaney A, Starr TN, Dingens AS, Chen EC, Chen R, Case B,
Sutton R, Gilchuk P, Rodriguez J, Armstrong E, Gainza C, Nargi R, Binshtein E,
Xie X, Zhang X, Shi PY, Logue J, Weston S, McGrath M, Frieman M, Brady T, Tuffy
K, Bright H, Loo YM, McvTamney P, Esser M, Carnahan R, Diamond M, Bloom J, Crowe
JE. Genetic and structural basis for recognition of SARS-CoV-2 spike protein by
a two-antibody cocktail. bioRxiv [Preprint]. 2021 Mar 1:2021.01.27.428529. doi:
10.1101/2021.01.27.428529. Update in: Nat Microbiol. 2021 Sep 21;: PMID:
33532768; PMCID: PMC7852235.

18: Saadat S, Rikhtegaran Tehrani Z, Logue J, Newman M, Frieman MB, Harris AD,
Sajadi MM. Binding and Neutralization Antibody Titers After a Single Vaccine
Dose in Health Care Workers Previously Infected With SARS-CoV-2. JAMA. 2021 Apr
13;325(14):1467-1469. doi: 10.1001/jama.2021.3341. PMID: 33646292; PMCID:
PMC7922233.

19: Alter G, Gorman M, Patel N, Guebre-Xabier M, Zhu A, Atyeo C, Pullen K, Loos
C, Goez-Gazi Y, Carrion R Jr, Tian JH, Yuan D, Bowman K, Zhou B, Maciejewski S,
McGrath M, Logue J, Frieman M, Montefiori D, Schendel S, Saphire EO,
Lauffenburger D, Greene A, Portnoff A, Massare M, Ellingsworth L, Glenn G, Smith
G, Mann C, Amanat F, Krammer F. Collaboration between the Fab and Fc contribute
to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine
with Matrix-M™ vaccination. Res Sq [Preprint]. 2021 Feb 15:rs.3.rs-200342. doi:
10.21203/rs.3.rs-200342/v1. Update in: Cell Rep Med. 2021 Aug 31;:100405. PMID:
33619473; PMCID: PMC7899467.

20: Gorman MJ, Patel N, Guebre-Xabier M, Zhu A, Atyeo C, Pullen KM, Loos C,
Goez-Gazi Y, Carrion R Jr, Tian JH, Yaun D, Bowman K, Zhou B, Maciejewski S,
McGrath ME, Logue J, Frieman MB, Montefiori D, Mann C, Schendel S, Amanat F,
Krammer F, Saphire EO, Lauffenburger D, Greene AM, Portnoff AD, Massare MJ,
Ellingsworth L, Glenn G, Smith G, Alter G. Collaboration between the Fab and Fc
contribute to maximal protection against SARS-CoV-2 in nonhuman primates
following NVX-CoV2373 subunit vaccine with Matrix-M™ vaccination. bioRxiv
[Preprint]. 2021 Feb 5:2021.02.05.429759. doi: 10.1101/2021.02.05.429759. Update
in: Cell Rep Med. 2021 Aug 31;:100405. PMID: 33564763; PMCID: PMC7872351.

21: Sivapalasingam S, Saviolakis GA, Kulcsar K, Nakamura A, Conrad T, Hassanein
M, Sumner G, Elango C, Kamal MA, Eng S, Kyratsous CA, Musser BJ, Frieman M,
Kantrowitz J, Weinreich DM, Yancopoulos G, Stahl N, Lipsich L. Human Monoclonal
Antibody Cocktail for the Treatment or Prophylaxis of Middle Eastern Respiratory
Syndrome Coronavirus (MERS-CoV). J Infect Dis. 2021 Jan 28:jiab036. doi:
10.1093/infdis/jiab036. Epub ahead of print. PMID: 33507266; PMCID: PMC7928873.

22: Tian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, Logue J, Portnoff
AD, Norton J, Guebre-Xabier M, Zhou B, Jacobson K, Maciejewski S, Khatoon R,
Wisniewska M, Moffitt W, Kluepfel-Stahl S, Ekechukwu B, Papin J, Boddapati S,
Jason Wong C, Piedra PA, Frieman MB, Massare MJ, Fries L, Bengtsson KL, Stertman
L, Ellingsworth L, Glenn G, Smith G. SARS-CoV-2 spike glycoprotein vaccine
candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat
Commun. 2021 Jan 14;12(1):372. doi: 10.1038/s41467-020-20653-8. PMID: 33446655;
PMCID: PMC7809486.

23: Puhl AC, Fritch EJ, Lane TR, Tse LV, Yount BL, Sacramento CQ, Tavella TA,
Costa FTM, Weston S, Logue J, Frieman M, Premkumar L, Pearce KH, Hurst BL,
Andrade CH, Levi JA, Johnson NJ, Kisthardt SC, Scholle F, Souza TML, Moorman NJ,
Baric RS, Madrid P, Ekins S. Repurposing the Ebola and Marburg Virus Inhibitors
Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and
Potential Mechanisms. bioRxiv [Preprint]. 2020 Dec 2:2020.12.01.407361. doi:
10.1101/2020.12.01.407361. Update in: ACS Omega. 2021 Mar 10;6(11):7454-7468.
PMID: 33299990; PMCID: PMC7724658.

24: Weston S, Baracco L, Keller C, Matthews K, McGrath ME, Logue J, Liang J,
Dyall J, Holbrook MR, Hensley LE, Jahrling PB, Yu W, MacKerell AD Jr, Frieman
MB. The SKI complex is a broad-spectrum, host-directed antiviral drug target for
coronaviruses, influenza, and filoviruses. Proc Natl Acad Sci U S A. 2020 Dec
1;117(48):30687-30698. doi: 10.1073/pnas.2012939117. Epub 2020 Nov 12. PMID:
33184176; PMCID: PMC7720140.

25: 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.

26: 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.

27: 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 Apr 13;: PMID: 33024967; PMCID: PMC7536870.

28: 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.

29: 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.

30: 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. PMID:
32935104; PMCID: PMC7491518.

31: 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.

32: Funnell SGP, Dowling WE, Muñoz-Fontela C, Gsell PS, Ingber DE, Hamilton GA,
Delang L, Rocha-Pereira J, Kaptein S, Dallmeier KH, Neyts J, Rosenke K, de Wit
E, Feldmann H, Maisonnasse P, Le Grand R, Frieman MB, Coleman CM. Emerging
preclinical evidence does not support broad use of hydroxychloroquine in
COVID-19 patients. Nat Commun. 2020 Aug 26;11(1):4253. doi:
10.1038/s41467-020-17907-w. PMID: 32848158; PMCID: PMC7450055.

33: 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.

34: 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 In Vitro and SARS-CoV In Vivo. J
Virol. 2020 Oct 14;94(21):e01218-20. doi: 10.1128/JVI.01218-20. PMID: 32817221;
PMCID: PMC7565640.

35: 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.

36: 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.

37: 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; PMCID: PMC7263075.

38: 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.

39: 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.

40: 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.

41: 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.

42: 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.

43: 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.

44: 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.

45: 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.

46: 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.

47: 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.

48: 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.

49: 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.

50: 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.

51: 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.

52: 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.

53: 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.

54: 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.

55: 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.

56: 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.

57: 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.

58: 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.

59: 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.

60: 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.

61: Frieman M, Sola I, Enjuanes L. Virus Research. Foreword. Nidoviruses II.
Virus Res. 2015 Apr 16;202:1-2. doi: 10.1016/j.virusres.2015.05.013. PMID:
26025418; PMCID: PMC7133811.

62: 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.

63: 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.

64: 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.

65: 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.

66: 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.

67: 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.

68: 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.

69: 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.

70: 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.

71: 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.

72: 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.

73: 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.

74: 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.

75: 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.

76: 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.

77: 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.

78: 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.

79: 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.

80: 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.

81: 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.

82: 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.

83: 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.

84: 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.

85: 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.

86: 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.

87: Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris
MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K,
Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV,
Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan
L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R,
Iraqi FA, Pomp D, Threadgill D, de Villena FP, Churchill GA. Genetic analysis of
complex traits in the emerging Collaborative Cross. Genome Res. 2011
Aug;21(8):1213-22. doi: 10.1101/gr.111310.110. Epub 2011 Mar 15. PMID: 21406540;
PMCID: PMC3149489.

88: 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.

89: 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.

90: 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.

91: 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.

92: 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.

93: 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.

94: Day CW, Baric R, Cai SX, Frieman M, Kumaki Y, Morrey JD, Smee DF, Barnard
DL. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating
antiviral agents in vitro and in vivo. Virology. 2009 Dec 20;395(2):210-22. doi:
10.1016/j.virol.2009.09.023. Epub 2009 Oct 22. PMID: 19853271; PMCID:
PMC2787736.

95: 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.

96: 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.

97: 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.

98: 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.

99: 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.

100: 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.

101: 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.

102: 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.

103: 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.

104: 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.

105: 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.

106: 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.

107: 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.

108: 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.

109: 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.

110: 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.

111: Frieman M, Chen ZJ, Saez-Vasquez J, Shen LA, Pikaard CS. RNA polymerase I
transcription in a Brassica interspecific hybrid and its progenitors: Tests of
transcription factor involvement in nucleolar dominance. Genetics. 1999
May;152(1):451-60. doi: 10.1093/genetics/152.1.451. PMID: 10224274; PMCID:
PMC1460595.

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.