【摘 要】
：
Although the spread of SARS-CoV,which caused the pandemic of 2002-2003,was effectively contained within a few months,the recent isolation of zoonotic strains thought to be the reservoir for SARS-CoV a
【机 构】
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Center for Pharmaceutical Biotechnology University of Illinois at Chicago USA
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
Although the spread of SARS-CoV,which caused the pandemic of 2002-2003,was effectively contained within a few months,the recent isolation of zoonotic strains thought to be the reservoir for SARS-CoV accentuates the potential for future retransmissions of SARS-CoV.The development of novel antivirals against SARS-CoV is therefore an important safeguard against future outbreaks and pandemics,but antivirals effective against SARS-CoV have yet to be developed.Two cysteine proteases within the polyprotein,a papain-like protease (PLpro) and a 3C-like protease (3CLpro),that catalyze their own release and that of the other nsps from the polyprotein,and initiate virus-mediated RNA replication,constitute excellent targets for antiviral development.Using novel computational screening approaches that incorporate protein flexibility,along with high throughput screening,we have identified initial leads against both SARS-CoV PLpro and 3CLpro.Further synthetic development has produced candidate therapeutics with nanomolar enzymatic inhibition and micromolar cell culture antiviral efficacy.Mutation resistance suggests that combination inhibitors against both targets will be most effective.Select leads also show efficacy against other coronavirus species,providing potential for future broad-spectrum antiviral development.
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