betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802476811  1 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA 80
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 1802476811 81 TLQ 83
Cdd:cd21827   81 VLQ 83

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802476811  1 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA 80
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 1802476811 81 TLQ 83
Cdd:cd21827   81 VLQ 83

betacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of betacoronaviruses including the highly pathogenic Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder; the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802476811  1 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA 80
Cdd:cd21827    1 SKLTDVKCTSVVLLSVLQQLHVESNSKLWAYCVKLHNDILAAKDPTEAFEKFVSLLSVLLSFPGAVDLDALCSELLDNPT 80

                 ...
gi 1802476811 81 TLQ 83
Cdd:cd21827   81 VLQ 83

coronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of alpha-, beta-, gamma- and deltacoronaviruses, including highly pathogenic betacoronaviruses such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV), SARS-CoV2 (also called 2019 novel CoV or 2019-nCoV), and Middle East respiratory syndrome-related (MERS) CoV. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802476811  1 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA 80
Cdd:cd21811    1 SKLTDVKCTAVVLLSLLQKLRVESNSKLWKQCVQLHNDILLAKDTTEVFEKLVSLLSVLLSMQGAVDLNRLCEEMLENRA 80

                 ...
gi 1802476811 81 TLQ 83
Cdd:cd21811   81 VLQ 83

gammacoronavirus non-structural protein 7; This model represents the non-structural protein 7 (Nsp7) of gammacoronaviruses that include Avian infectious bronchitis virus (IBV) and Canada goose coronavirus (CGCoV), among others. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Upon processing of the Nsp7-10 region by protease M (Mpro), the released four small proteins Nsp7, Nsp8, Nsp9 and Nsp10 form functional complexes with CoV core enzymes and stimulate replication. Most importantly, a complex of Nsp7 with Nsp8 has been shown to activate and confer processivity to the RNA-synthesizing activity of Nsp12, the RNA-dependent RNA-polymerase (RdRp); in SARS-CoV, point mutations in the NSP7- or NSP8-coding region have been shown to delay virus growth. Nsp7 and Nsp8 cooperate in activating the primer-dependent activity of the Nsp12 RdRp such that the level of their association may constitute a limiting factor for obtaining a high RNA polymerase activity. The subsequent Nsp7/Nsp8/Nsp12 polymerase complex is then able to associate with an active bifunctional Nsp14, which includes N-terminal 3' to 5' exoribonuclease (ExoN) and C-terminal N7-guanine cap methyltransferase (N7-MTase) activities, thus representing a unique coronavirus Nsp assembly that incorporates RdRp, exoribonuclease, and N7-MTase activities. Interaction of Nsp7 with Nsp8 appears to be conserved across the coronavirus family, making these proteins interesting drug targets. Nsp7 has a 4-helical bundle conformation which is strongly affected by its interaction with Nsp8, especially where it concerns alpha-helix 4. SARS-CoV Nsp7 forms a 8:8 hexadecameric supercomplex with Nsp8 that adopts a hollow cylinder-like structure with a large central channel and positive electrostatic properties in the cylinder, while Feline infectious peritonitis virus Nsp7 forms a 2:1 heterotrimer with Nsp8. Regardless of their oligomeric structure, the Nsp7/Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1802476811  1 SKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHNDILLAKDTTEAFEKMVSLLSVLLSMQGAVDINKLCEEMLDNRA 80
Cdd:cd21828    1 SKLTDVKCTTVVLMQLLTKLNVEANSKMHKYLVELHNKILASDDVVECMDNLLGMLVTLLCIDSTIDLSEYCDDILKRST 80

                 ...
gi 1802476811 81 TLQ 83
Cdd:cd21828   81 VLQ 83