Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019(COVID-19)and instigated a widespread fear,threatening global health safety.To date,no licensed antiviral drugs or vaccines are available ...Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019(COVID-19)and instigated a widespread fear,threatening global health safety.To date,no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies.During this urgent situation,computational drug discovery methods provide an alternative to tiresome high-throughput screening,particularly in the hit-to-lead-optimization stage.Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery.In this work,we present potential compounds that specifically target SARS-CoV-2 vital proteins,including the main protease,Nsp12 RNA polymerase and Nsp13 helicase.An integrative virtual screening and molecular dynamics simulations approach has facilitated the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds.Moreover,the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis.Although the current study lacks experimental validation,the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.展开更多
H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8...H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8 virus was found on a dog which differentiated the virus from existing H3N2 canine virus. At this point, we wanted to find out why H5N8 was self-medicated in dogs and whether H5N8 would cross species boundaries and be fatal to dogs or other species. While H5N1 is avian influenza like H5N8, many cases of fatal infections among dogs caused by H5N1 have been reported. Another kind of avian influenza, H3N2 is most common type of canine influenza in Asia. With the use of decision tree and apriori algorithm, we could find out characteristics of H5N8 by comparing it with H5N1 and H3N2.展开更多
基金This study was supported by IRO scholarship Ph.D.Grant.
文摘Recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019(COVID-19)and instigated a widespread fear,threatening global health safety.To date,no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are under way to test possible therapies.During this urgent situation,computational drug discovery methods provide an alternative to tiresome high-throughput screening,particularly in the hit-to-lead-optimization stage.Identification of small molecules that specifically target viral replication apparatus has indicated the highest potential towards antiviral drug discovery.In this work,we present potential compounds that specifically target SARS-CoV-2 vital proteins,including the main protease,Nsp12 RNA polymerase and Nsp13 helicase.An integrative virtual screening and molecular dynamics simulations approach has facilitated the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds.Moreover,the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis.Although the current study lacks experimental validation,the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.
文摘H3N2, H5N1 and H5N8 virus were wide-spread epidemic in South Korea. Especially in 2014 Korea, the serious outbreak of avian influenza caused by H5N8 took place, effecting not only birds but also dogs. Antibody of H5N8 virus was found on a dog which differentiated the virus from existing H3N2 canine virus. At this point, we wanted to find out why H5N8 was self-medicated in dogs and whether H5N8 would cross species boundaries and be fatal to dogs or other species. While H5N1 is avian influenza like H5N8, many cases of fatal infections among dogs caused by H5N1 have been reported. Another kind of avian influenza, H3N2 is most common type of canine influenza in Asia. With the use of decision tree and apriori algorithm, we could find out characteristics of H5N8 by comparing it with H5N1 and H3N2.
