Rational design of a new class of protease inhibitors for the potential treatment of coronavirus diseases

The coronavirus main protease, Mpro, is a key protein in the virus life cycle and a major drug target. Based on crystal structures of SARSCoV2 Mpro complexed with peptidomimetic inhibitors, we recognized a binding characteristic shared with proline-containing inhibitors of hepatitis C virus protease. Initial tests showed that this subclass of HCV protease inhibitors indeed exhibited activity against Mpro. Postulating a benefit for a preorganized backbone conformation, we designed new ketoamide-based Mpro inhibitors based on central proline rings. One of the designed compounds, ML1000, inhibits Mpro with low-nanomolar affinity and suppresses SARSCoV2 viral replication in human cells at sub-micromolar concentrations. Our findings identify ML1000 as a promising new pre-organized scaffold for the development of anti-coronavirus drugs.

Estimate of airborne transmission of SARS-CoV-2 using real time tracking of health care workers.

BACKGROUNDWhether and to what degree SARS-CoV-2 is spread via the airborne route is unknown. Using data collected from health care worker interactions with hospitalized patients with COVID-19 illness, we calculated the transmissibility of SARS-CoV-2 via the airborne route. OBJECTIVES/METHODSHealthcare worker interaction with SARS-CoV-2 infected patients were tracked using a real time location system between March 18 and March 31. A value for q, the transmissibility expressed as quanta per hour, was estimated using a well-established model for airborne transmission. RESULTSSARS-CoV-2 infection prevalence among tracked HCWs was 2.21% (0.07-4.35). Transmissibility was estimated to be 0.225 quanta per hour, well below other well-characterized airborne pathogens. Simulations demonstrated that risk of infection is substantially reduced with increased ventilation of rooms. CONCLUSIONSOverall, our findings suggest that SARS-CoV-2 is not well transmitted via the airborne route in controlled conditions. We speculate that SARS-CoV-2 may be only opportunistically airborne, with most transmission occurring via droplet methods. One Sentence SummaryWe calculated the airborne transmissibility (q) of SARS-CoV-2 and the impact of masks and ventilation in a hospital setting.