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Therapeutic Interventions * No approved drugs, immune therapeutics and vacc against any group 2b coronavirus * Experimental Drugs (nsp12-RdRp target) -- Remdesivir-ribonucleoside inhibitor -- EIDD-1931-(b-D-N*-hydroxycytidine)-ribonucleoside inhibito -- Combination lopinavir, ritonavir, and interferon beta again -- Therapeutic antibodies (MERS-CoV) Conservation of key RdRp motif residues Motif G Motif F Motif A Motif B Motif C M Positioning of the Nucleotide binding Nucleotide binding. Nucieotige binding tit an Stabiliz 5S template strand Doty! active ste PDCOV DKSAGYPFUKLGK LKYAISARDRARTVAGY PILVOWDYPKCDRSM COTSSCDATIAYANSVENILQVVSANVATELST FOLMILSDDOVACID AKAGAVADL 229E NKSAGWPLNKFGK LKYAISGKERARTVOGV PKLMGWDYPKCDRAM GOTTSGDATTAYANSVENIFQAVSSNINCVLSV FSMMILSDOGVVCYN ABLGYIADI NL63 DKSAGYPFNKFGK LKYAISAKNRARTVAGY PVLMGWDYPKCDRAM GGTSSGDATTAFANSVENICQAVSANVCALMSC FSMMILSDDGVYCYN ASKGYIANIS 0C43 DKSAGYPFNKPGR LKYAISAKNRARTVAGY PVLMGWDYPKCDRAM GGTSSGDAPTAPANEVPNICQAVSANVCALMSC PSMMILSDOGVVCYN ASKGY IANT MHV DKSAGYPFNKFGK LKYAISAKNRARTVAGY PVLMGWDY PKCDRAM GGTSSGOATTAPANSVPNICQAVSANVCSLMAC FSMMILSDDGVVCYN ASKGY IANIS KU] DKSAGYPFNKFGK LEYAISAKNRARTVAGV PVLMGWDYPKCORAM GGTSSGOATTAFANSVENICQAVTANVCSLMAC FSMMILSDDGVVCYN ASKGYIANIS MERS DKSAGHPFNKFGK LKYAISAKNRARTVAGV PHLMGWDYPRCDRAM GGTSSGDATTAYANSVENILOATTANVSALMGA ILSDDGVVCYN AAKGYIAGI HKU9-4 DKSAGFPFNKFGK LKYAISAKNRARTVAGY PHLMGNDYPKCDRAM GGTSSGDSTTAYANSVFNICQAVSANLNTP! ILSDDGVVCYN AQKGYVADI nCoV-2019 DKSAGFPFNKWGK LKYAISARNRARTVAGY PHLMGWDYPKCDRAM GGTSSGDATTATANGVPNICQAVTANVNALLST FSMMILSDDAVVCFN ASQGLVASI HKU3 DKSAGEPFNKWGK LKXAISAKRNRARTVAGY PHLMGWDYPKCDRAM GOTSSGDATTAYANSVPNICQAVTANVNALLST FSMMILSDDAVVCIN AAQGLVASI SARS-COV DKSAGFPFNEWGK LKYAISAKNRARTVAGY PHLMGWDYPKCDRAM GGTSSGDATTAYANSVFNICQAVTANVNALLST FSMMILSDDAVVCYN AAQGLVASI SHCO14 DKSAGFPFNKWGK LKYAISAKNRARTVAGY PHLMGWDYPKCDRAM GOTSSGDATTA' ISVFNICOAVTANVNALLST FSMMILSDDAVVCYN AAQGLVASI a ee f I oe a e '560 612 ere 10 753 mee 711 Position in SARS-CoV i V553. in MHV and VSS: SARS-CoV in Mont F Sheahan et al., Nature Communications 11, 222 (2020) Sheahan et al., Sci Trans! M