VETERINARY QUARTERLY⊙乃 pplb 1 ireGenome of novelcronirs Comparative pike (5)proteinseqence length of diferent Additionally,for S-gene,per cent similarity range past de ades.But the degree of cross-protection pro patter was eva ted amin acid ba by s vaccines s greatly limited due to 0199 and US 81 8%6 and 77 0 to 78 196 for 2019-nCov isolate 013 As for MERS and SAp Bat SARS-like Covs and other SABS like Covs there is no licensed specific antiviral t respectively.The per cent identity with human cor- vaccine available till now.However.few of the onavirus isolate HCoV-OC43 was also found lower advan in developing vaccines and ther (28.0%)(Supplementary data 2) eutic SARS-CoV and ERS-Co nuc sed per 20于m h t to tackle thepr genetic tree the 2019-nCov isolates classified insub navirus pa would take some time,therefore genus Sarbecovirus and the sequences from CRCov, till then we need to rely extensively on enforcing BCoV and HCoV-OC43 isolates clustered in subgenus ffective pre tion and control n Embecovirus nov the enomic analysis. the gene of 2019 of th with othe e in snike fo encoded by 2019-nCoy compared with the Bat ein or s tein (Graham et al.2013).This is mainl SARS-like CoVs,SARS-CoV,and MERS-CoV is depicted because of the fact S protein s the majo in Figure 5.The length of 'S'protein of nCoV is l nducer eutralizing antib (Jiang et a ids)tha ner tw virus (SAR nd ar tiviral ugs that ar -12 Cov ha det. full-lenath s protein viral vecto ased ya at the N-terminal region.along with four changes in cine,DNA-based vaccine, recombinant s protein the receptor binding motif inside the receptor bind- based and recombinant RBD protein-based vaccines ing domain in comparison with SARS-CoV (Zhou Whereas S protein based antiviral therapi et al.2020).Several previous studies have shown the ACE2 hib to th Du e 200 SARS-CoVs hav options have proven efficacy in the in vitro studie most of these haven't undergone random and Munster 2020).A recent finding proves that the animal or human trials and hence are of limite binding capacity of nCov S'protein with humar ent ACE2 is the nanto-numa o an 2020 disease.It also has anti-coronavirus activity due its inhibitory action on the SARS-CoV and MERS-Cov replication (Sheahan et al.2017).At present,effort 5.Advances and prospects in developing vaccines and therapeutics are being made to identify and develop monodlona s have been at are therapy a93C0 d Additionally, for S-gene, per cent similarity range pattern was evaluated in amino acid based index where 2019-nCoV isolates from China and USA were 100% identical. The range varied between 81.2 to 81.8% and 77.0 to 78.1% for 2019-nCoV isolates with Bat_SARS-like CoVs and other SARS like CoVs, respectively. The per cent identity with human cor￾onavirus isolate HCoV-OC43 was also found lower (28.0%) (Supplementary data 2). Overall, the nucleotide and amino acid based per cent identities indicate toward highly diverged nature of novel coronaviruses. To note, in the phylo￾genetic tree the 2019-nCoV isolates classified in sub￾genus Sarbecovirus and the sequences from CRCoV, BCoV and HCoV-OC43 isolates clustered in subgenus Embecovirus. In the genomic analysis, the S gene of 2019- nCoVs was found to exhibit lower sequence identity with other Betacoronaviruses. Difference in spike pro￾tein encoded by 2019-nCoV compared with the Bat SARS-like CoVs, SARS-CoV, and MERS-CoV is depicted in Figure 5. The length of ‘S’ protein of nCoV is lon￾ger (1282 amino acids) than other two viruses (SARS- 1255 amino acid and BatSL-1246 amino acids) under the same Sarbecovirus subgenus. The ‘S’ protein of nCoV has been detected with three short insertions at the N-terminal region, along with four changes in the receptor binding motif inside the receptor bind￾ing domain in comparison with SARS-CoV (Zhou et al. 2020). Several previous studies have shown the usage of different receptors for CoVs like human ACE2 for SARS-CoV and CD26 for MERS-CoV (Lu et al. 2020). Identical motifs and residues to that of SARS-CoVs have been identified in the nCoV, yet they show divergence based on phylogeny (Letko and Munster 2020). A recent finding proves that the binding capacity of nCoV ‘S’ protein with human ACE2 is as efficient as SARS-CoV, which further pro￾motes the human-to-human transmission (Letko and Munster 2020). 5. Advances and prospects in developing vaccines and therapeutics Several attempts have been made to develop vac￾cines against human coronavirus infection in the past decades. But the degree of cross-protection pro￾vided by such vaccines is greatly limited due to the extensive diversity in antigenic variants even within the strains of a phylogenetic sub-cluster (Graham et al. 2013). As for MERS and SARS coronaviruses, there is no licensed specific antiviral treatment or vaccine available till now. However, few of the advances made in developing vaccines and thera￾peutics for SARS-CoV and MERS-CoV could be exploited for the countering 2019-nCoV. But since the efforts to design and develop any vaccine or antiviral agent to tackle the presently emerging cor￾onavirus pathogen would take some time, therefore till then we need to rely extensively on enforcing highly effective prevention and control measures to minimize the risk of 2019-nCoV transmission and spread to the best feasible extent (Cheng et al. 2020). Majority of the vaccines that are being devel￾oped for coronaviruses targets the Spike glycopro￾tein or S protein (Graham et al. 2013). This is mainly because of the fact that S protein is the major inducer of neutralizing antibodies (Jiang et al. 2005). Several kinds of vaccines and antiviral drugs that are based on S protein have been previously evaluated. Among them, the S protein-based vaccines include full-length S protein vaccines, viral vector-based vac￾cine, DNA-based vaccine, recombinant S protein￾based and recombinant RBD protein-based vaccines. Whereas S protein based antiviral therapies include RBD–ACE2 blockers, S cleavage inhibitors, fusion core blockers, neutralizing antibodies, protease inhib￾itors, S protein inhibitors, and small interfering RNAs (Du et al. 2009). Even though such therapeutic options have proven efficacy in the in vitro studies, however most of these haven’t undergone random￾ized animal or human trials and hence are of limited use in our present 2019-nCoV scenario. Remdesivir is a novel nucleotide analog prodrug that was intended to be used for the treatment of Ebola virus disease. It also has anti-coronavirus activity due to its inhibitory action on the SARS-CoV and MERS-CoV replication (Sheahan et al. 2017). At present, efforts are being made to identify and develop monoclonal antibodies that are specific and effective against 2019-nCoV. Combination therapy with 2019-nCoV specific monoclonal antibodies and remdesivir can Figure 5. Genome organization of novel coronavirus. Comparative spike (S) protein sequence length of different Betacoronaviruses is depicted. VETERINARY QUARTERLY 73