Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV

被引:576
作者
Morse, Jared S. [1 ]
Lalonde, Tyler [1 ]
Xu, Shiqing [1 ]
Liu, Wenshe Ray [1 ]
机构
[1] Texas A&M Univ, Dept Chem, Texas A&M Drug Discovery Lab, College Stn, TX 77843 USA
基金
美国国家卫生研究院;
关键词
antiviral agents; coronavirus; 2019-nCoV; SARS; spike proteins; RdRp; 3CLpro; PAPAIN-LIKE PROTEASE; RECEPTOR-BINDING DOMAIN; SARS-CORONAVIRUS; AURINTRICARBOXYLIC ACID; SPIKE PROTEIN; COV; VACCINE; POTENT; IDENTIFICATION; RIBAVIRIN;
D O I
10.1002/cbic.202000047
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
With the current trajectory of the 2019-nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better-studied cousin, SARS-CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA-dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS-CoV. Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad-spectrum anti-coronaviral agents for future epidemics.
引用
收藏
页码:730 / 738
页数:9
相关论文
共 48 条
[1]   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)
[2]   Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study [J].
Al-Tawfiq, Jaffar A. ;
Momattin, Hisham ;
Dib, Jean ;
Memish, Ziad A. .
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2014, 20 :42-46
[3]   The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds [J].
Baez-Santos, Yahira M. ;
St John, Sarah E. ;
Mesecar, Andrew D. .
ANTIVIRAL RESEARCH, 2015, 115 :21-38
[4]   Programmed ribosomal frameshifting in decoding the SARS-CoV genome [J].
Baranov, PV ;
Henderson, CM ;
Anderson, CB ;
Gesteland, RF ;
Atkins, JF ;
Howard, MT .
VIROLOGY, 2005, 332 (02) :498-510
[5]   Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus [J].
Cavanagh, D .
AVIAN PATHOLOGY, 2003, 32 (06) :567-582
[6]  
Chen Xin, 2009, Antivir Chem Chemother, V19, P151
[7]   Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus [J].
Cheng, Kai-Wen ;
Cheng, Shu-Chun ;
Chen, Wei-Yi ;
Lin, Min-Han ;
Chuang, Shang-Ju ;
Cheng, I-Hsin ;
Sun, Chiao-Yin ;
Chou, Chi-Yuan .
ANTIVIRAL RESEARCH, 2015, 115 :9-16
[8]   Adverse effects of ribavirin and outcome in severe acute respiratory syndrome - Experience in two medical centers [J].
Chiou, HE ;
Liu, CL ;
Buttrey, MJ ;
Kuo, HP ;
Lin, HW ;
Kuo, HT ;
Lu, YT .
CHEST, 2005, 128 (01) :263-272
[9]   PREPARATION AND ANTI-HIV ACTIVITIES OF AURINTRICARBOXYLIC ACID FRACTIONS AND ANALOGS - DIRECT CORRELATION OF ANTIVIRAL POTENCY WITH MOLECULAR-WEIGHT [J].
CUSHMAN, M ;
WANG, PL ;
CHANG, SH ;
WILD, C ;
DECLERCQ, E ;
SCHOLS, D ;
GOLDMAN, ME ;
BOWEN, JA .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :329-337
[10]   The spike protein of SARS-CoV - a target for vaccine and therapeutic development [J].
Du, Lanying ;
He, Yuxian ;
Zhou, Yusen ;
Liu, Shuwen ;
Zheng, Bo-Jian ;
Jiang, Shibo .
NATURE REVIEWS MICROBIOLOGY, 2009, 7 (03) :226-236