Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV

被引：1168

作者：

Sheahan, Timothy P. ^{[1
]}

Sims, Amy C. ^{[1
]}

Leist, Sarah R. ^{[1
]}

Schafer, Alexandra ^{[1
]}

Won, John ^{[1
]}

Brown, Ariane J. ^{[1
]}

Montgomery, Stephanie A. ^{[2
]}

Hogg, Alison ^{[3
]}

Babusis, Darius ^{[3
]}

Clarke, Michael O. ^{[3
]}

Spahn, Jamie E. ^{[3
]}

Bauer, Laura ^{[3
]}

Sellers, Scott ^{[3
]}

Porter, Danielle ^{[3
]}

Feng, Joy Y. ^{[3
]}

Cihlar, Tomas ^{[3
]}

Jordan, Robert ^{[3
]}

Denison, Mark R. ^{[4
]}

Baric, Ralph S. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[2] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA

[3] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA

[4] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Dept Pediat Infect Dis, Nashville, TN USA

来源：

NATURE COMMUNICATIONS | 2020年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

EAST RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS; VIRUS; LOPINAVIR/RITONAVIR; INFECTION; INHIBITORS; RIBAVIRIN; EXPOSURE; FEATURES; LAMBDA;

D O I：

10.1038/s41467-019-13940-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Middle East respiratory syndrome coronavirus (MERS-CoV) is the causative agent of a severe respiratory disease associated with more than 2468 human infections and over 851 deaths in 27 countries since 2012. There are no approved treatments for MERS-CoV infection although a combination of lopinavir, ritonavir and interferon beta (LPV/RTV-IFNb) is currently being evaluated in humans in the Kingdom of Saudi Arabia. Here, we show that remdesivir (RDV) and IFNb have superior antiviral activity to LPV and RTV in vitro. In mice, both prophylactic and therapeutic RDV improve pulmonary function and reduce lung viral loads and severe lung pathology. In contrast, prophylactic LPV/RTV-IFNb slightly reduces viral loads without impacting other disease parameters. Therapeutic LPV/RTV-IFNb improves pulmonary function but does not reduce virus replication or severe lung pathology. Thus, we provide in vivo evidence of the potential for RDV to treat MERS-CoV infections.

引用

页数：14

共 56 条

[1] Mouse Models of Acute Respiratory Distress Syndrome: A Review of Analytical Approaches, Pathologic Features, and Common Measurements [J].

Aeffner, Famke ;

Bolon, Brad ;

Davis, Ian C. .

TOXICOLOGIC PATHOLOGY, 2015, 43 (08) :1074-1092

[2] Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease [J].

Agostini, Maria L. ;

Andres, Erica L. ;

Sims, Amy C. ;

Graham, Rachel L. ;

Sheahan, Timothy P. ;

Lu, Xiaotao ;

Smith, Everett Clinton ;

Case, James Brett ;

Feng, Joy Y. ;

Jordan, Robert ;

Ray, Adrian S. ;

Cihlar, Tomas ;

Siegel, Dustin ;

Mackman, Richard L. ;

Clarke, Michael O. ;

Baric, Ralph S. ;

Denison, Mark R. .

MBIO, 2018, 9 (02)

[3]

[Anonymous], 2018, MIDDL E RESP SYNDR C

[4]

Arabi Y. M., 2016, MERS COV INFECT TREA

[5]

Arabi Y. M., 2019, TWITTER ACCOUNT MIRA

[6] Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial [J].

Arabi, Yaseen M. ;

Alothman, Adel ;

Balkhy, Hanan H. ;

Al-Dawood, Abdulaziz ;

AlJohani, Sameera ;

Al Harbi, Shmeylan ;

Kojan, Suleiman ;

Al Jeraisy, Majed ;

Deeb, Ahmad M. ;

Assiri, Abdullah M. ;

Al-Hameed, Fahad ;

AlSaedi, Asim ;

Mandourah, Yasser ;

Almekhlafi, Ghaleb A. ;

Sherbeeni, Nisreen Murad ;

Elzein, Fatehi Elnour ;

Memon, Javed ;

Taha, Yusri ;

Almotairi, Abdullah ;

Maghrabi, Khalid A. ;

Qushmaq, Ismael ;

Al Bshabshe, Ali ;

Kharaba, Ayman ;

Shalhoub, Sarah ;

Jose, Jesna ;

Fowler, Robert A. ;

Hayden, Frederick G. ;

Hussein, Mohamed A. .

TRIALS, 2018, 19

[7]

Betaseron, 2015, HIGHL PRESCR INF

[8] Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase [J].

Brown, Ariane J. ;

Won, John J. ;

Graham, Rachel L. ;

Dinnon, Kenneth H., III ;

Sims, Amy C. ;

Feng, Joy Y. ;

Cihlar, Tomas ;

Denison, Mark R. ;

Baric, Ralph S. ;

Sheahan, Timothy P. .

ANTIVIRAL RESEARCH, 2019, 169

[9] Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus [J].

Chan, Jasper F. W. ;

Chan, Kwok-Hung ;

Kao, Richard Y. T. ;

To, Kelvin K. W. ;

Zheng, Bo-Jian ;

Li, Clara P. Y. ;

Li, Patrick T. W. ;

Dai, Jun ;

Mok, Florence K. Y. ;

Chen, Honglin ;

Hayden, Frederick G. ;

Yuen, Kwok-Yung .

JOURNAL OF INFECTION, 2013, 67 (06) :606-616

[10] Treatment With Lopinavir/Ritonavir or Interferon-β1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset [J].

Chan, Jasper Fuk-Woo ;

Yao, Yanfeng ;

Yeung, Man-Lung ;

Deng, Wei ;

Bao, Linlin ;

Jia, Lilong ;

Li, Fengdi ;

Xiao, Chong ;

Gao, Hong ;

Yu, Pin ;

Cai, Jian-Piao ;

Chu, Hin ;

Zhou, Jie ;

Chen, Honglin ;

Qin, Chuan ;

Yuen, Kwok-Yung .

JOURNAL OF INFECTIOUS DISEASES, 2015, 212 (12) :1904-1913

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