Abstract
Three types of new coronaviruses (CoVs) have been identified recently as the causative viruses for the severe pneumonia-like respiratory illnesses, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and corona-virus disease 2019 (COVID-19). Neither therapeutic agents nor vaccines have been developed to date, which is a major drawback in controlling the present global pandemic of COVID-19 caused by SARS coronavirus 2 (SARS-CoV-2) and has resulted in more than 20,439,814 cases and 744,385 deaths. Each of the 3C-like (3CL) proteases of the three CoVs is essential for the proliferation of the CoVs, and an inhibitor of the 3CL protease (3CLpro) is thought to be an ideal therapeutic agent against SARS, MERS, or COVID-19. Among these, SARS-CoV is the first corona-virus isolated and has been studied in detail since the first pandemic in 2003. This article briefly reviews a series of studies on SARS-CoV, focusing on the development of inhibitors for the SARS-CoV 3CLpro based on molecular interactions with the 3CL protease. Our recent approach, based on the structure-based rational design of a novel scaffold for SARS-CoV 3CLpro inhibitor, is also included. The achievements summarized in this short review would be useful for the design of a variety of novel inhibitors for corona-viruses, including SARS-CoV-2.
Highlights
IntroductionThe term coronavirus (CoV) is derived from the crown-like spikes on the surface of the virus
The term coronavirus (CoV) is derived from the crown-like spikes on the surface of the virus.CoVs are enveloped positive-strand RNA viruses that infect various vertebrates, including humans.In the 1960s, two human coronaviruses, the human alpha coronavirus 229E (HCoV-229E) and the human beta coronavirus OC43 (HCoV-OC43) were discovered as causative agents of disorders such as the common cold or respiratory illnesses of mild to moderate severity [1,2]
The inhibitor design briefly surveyed in this short review is a potential starting point for the development of anti-severe acute respiratory syndrome (SARS)-CoV agents; of note, most inhibitors described in this review have inhibitory potency against CoV as well as good physicochemical and pharmacodynamics properties necessary for in vivo use
Summary
The term coronavirus (CoV) is derived from the crown-like spikes on the surface of the virus. In 2012, a new respiratory illness similar to SARS, named Middle East respiratory syndrome (MERS), affected more than 1800 patients with a fatality rate of 36% [11,12] Even after these pandemics, no effective therapy has been developed for CoVs infections, and the present worldwide pandemic of corona-virus disease 2019 (COVID-19) has resulted in more than 20,439,814 cases and 744,385 deaths [13]. The sequence of SARS-CoV-2 3CLpro shares 96% homology with that of SARS-CoV 3CLpro , initially identified from the SARS causative coronavirus [20] These findings indicate that the studies on the SARS-CoV 3CLpro are robust bases for designing therapeutic agents for COVID-19. The protein chemistry of the target enzyme, SARS-CoV 3CLpro , is described in brief, as a basis for the structural analyses of protease-inhibitor interactions
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