Targeting genetic and chemical vulnerabilities of novel coronavirus SARS-CoV-2 [Added supplement: COVID-19 Variant Supplement]

The recent outbreak of the SARS-CoV-2 coronavirus in China and its continued international spread threatens to become a global pandemic. Although coronaviruses generally cause mild respiratory infections in humans, over the past 18 years, three animal-derived coronaviruses have emerged that cause much more severe disease: SARS-CoV, MERS-CoV, and the current SARS-CoV-2. Each of these emergent viruses cause substantially higher death rates than common coronavirus infections; the current estimate of the death rate due to COVID-19 syndrome caused by SARS-CoV-2 infection is ~2.5%. The main challenge in addressing these new coronavirus-associated outbreaks is a lack of suitable therapeutics to treat active disease (i.e., anti-viral drugs) or to prevent disease (i.e., appropriate vaccines). We propose to apply genomics-based tools and drug-screening platforms to rapidly pinpoint new targets for SARS-CoV-2 anti-viral agents and to identify candidate therapeutic compounds. Our team has deep expertise in anti-infective drug discovery, the application of genomics in identifying drug targets, and in the biology and biochemistry of RNA viruses such as SARS-CoV-2. Our project will identify new therapeutic strategies that may help to treat COVID-19 patients. These strategies will also help mitigate newly emergent coronavirus-associated diseases that will undoubtedly continue to cause outbreaks in the future.