Repurposing the HCV NS3-4A protease drug boceprevir as COVID-19 therapeutics

The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. De novo drug discovery takes years to move from idea and/or pre-clinic to market, and it is not a short-term solution for the current SARS-CoV-2 pandemic. Drug repurposing is perhaps the only short-term solution, while vaccination is a middle-term solution. Here, we describe the discovery path of the HCV NS3–4A protease inhibitors boceprevir and telaprevir as SARS-CoV-2 main protease (3CLpro) inhibitors. Based on our hypothesis that α-ketoamide drugs can covalently bind to the active site cysteine of the SARS-CoV-2 3CLpro, we performed docking studies, enzyme inhibition and co-crystal structure analyses and finally established that boceprevir, but not telaprevir, inhibits replication of SARS-CoV-2 and mouse hepatitis virus (MHV), another coronavirus, in cell culture. Based on our studies, the HCV drug boceprevir deserves further attention as a repurposed drug for COVID-19 and potentially other coronaviral infections as well

Search for Gamma-Ray and Neutrino Coincidences Using HAWC and ANTARES Data

In the quest for high-energy neutrino sources, the Astrophysical Multimessenger Observatory Net- work (AMON) has implemented a new search by combining data from the High Altitude Water Cherenkov (HAWC) observatory and the Astronomy with a Neutrino Telescope and Abyss environ- mental RESearch (ANTARES) neutrino telescope. Using the same analysis strategy as in a previous detector combination of HAWC and IceCube data, we perform a search for coincidences in HAWC and ANTARES events that are below the threshold for sending public alerts in each individual detector. Data were collected between July 2015 and February 2020 with a livetime of 4.39 years. Over this time period, 3 coincident events with an estimated false-alarm rate of $< 1$ coincidence per year were found. This number is consistent with background expectations