A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019-nCoV)

Abstract

During an outbreak of respiratory diseases including atypical pneumonia in Wuhan, a previously unknown β-coronavirus was detected in patients. The newly discovered coronavirus is similar to some β-coronaviruses found in bats but different from previously known SARS-CoV and MERS-CoV. High sequence identities and similarities between 2019-nCoV and SARS-CoV were found. In this study, we searched the homologous templates of all nonstructural and structural proteins of 2019-nCoV. Among the nonstructural proteins, the leader protein (nsp1), the papain-like protease (nsp3), the nsp4, the 3C-like protease (nsp5), the nsp7, the nsp8, the nsp9, the nsp10, the RNA-directed RNA polymerase (nsp12), the helicase (nsp13), the guanine-N7 methyltransferase (nsp14), the uridylate-specific endoribonuclease (nsp15), the 2'-O-methyltransferase (nsp16), and the ORF7a protein could be built on the basis of homology templates. Among the structural proteins, the spike protein (S-protein), the envelope protein (E-protein), and the nucleocapsid protein (N-protein) can be constructed based on the crystal structures of the proteins from SARS-CoV. It is known that PL-Pro, 3CL-Pro, and RdRp are important targets for design antiviral drugs against 2019-nCoV. And S protein is a critical target candidate for inhibitor screening or vaccine design against 2019-nCoV because coronavirus replication is initiated by the binding of S protein to cell surface receptors. It is believed that these proteins should be useful for further structure-based virtual screening and related computer-aided drug development and vaccine design.

Keywords: 2019-nCoV; BLAST algorithm; CLUSTAL analysis; MERS-CoV; SARS-CoV; coronavirus; homology modeling; sequence alignment.

Figure 1

Cartoon displayed models of ORF1ab related proteins constructed based on (A) 2HSX_A, (B) 2IDY_A, (C) 2ACF_A, (D) 2WCT_A, (E) 2KAF_A, (F) 5TI6_A, (G) 2K87_A, (H) 3VCB_A, (I) 5B6O_A, (J) 2AHM_A, (K) 2AHM_G, (L) 1UW7_A, (M) 5C8S_A, (N) 6NUR_A, (O) 6JYT_A, (P) 5C8S_B, (Q) 2H85_A, and (R) 3R24_A

Figure 2

Cartoon displayed models of proteins constructed based on (A) 6ACD_A, (B) 5X29_A, (C) 1YO4_A, (D) 1SSK_A, and (E) 2JW8_A