Genomic diversity and evolution, diagnosis, prevention, and therapeutics of the pandemic COVID-19 disease

Abstract

The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by a novel evolutionarily divergent RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus first emerged in Wuhan, China in December 2019, and subsequently spreaded around the world. Genomic analyses revealed that this zoonotic virus may be evolved naturally but not a purposefully manipulated laboratory construct. However, currently available data are not sufficient to precisely conclude the origin of this fearsome virus. Comprehensive annotations of the whole-genomes revealed hundreds of nucleotides, and amino acids mutations, substitutions and/or deletions at different positions of the ever changing SARS-CoV-2 genome. The spike (S) glycoprotein of SARS-CoV-2 possesses a functional polybasic (furin) cleavage site at the S1-S2 boundary through the insertion of 12 nucleotides. It leads to the predicted acquisition of 3-O-linked glycan around the cleavage site. Although real-time RT-PCR methods targeting specific gene(s) have widely been used to diagnose the COVID-19 patients, however, recently developed more convenient, cheap, rapid, and specific diagnostic tools targeting antigens or CRISPR-Cas-mediated method or a newly developed plug and play method should be available for the resource-poor developing countries. A large number of candidate drugs, vaccines and therapies have shown great promise in early trials, however, these candidates of preventive or therapeutic agents have to pass a long path of trials before being released for the practical application against COVID-19. This review updates current knowledge on origin, genomic evolution, development of the diagnostic tools, and the preventive or therapeutic remedies of the COVID-19. We also discussed the future scopes for research, effective management, and surveillance of the newly emerged COVID-19 disease.

Keywords: Diagnostics; Genetic diversity; Genome evolution; Therapeutics; Vaccines; SARS-CoV-2.

Figure 1. Genome organization of (A) SARS-CoV-2, (B) SARS-CoV and (C) MERS-CoV.

The genome of these three viruses comprises the 5′-untranslated region (5′-UTR), polyprotein with open reading frame (orf) 1a/b (blue box) representing non-structural proteins (nsp) for replication, structural proteins including S glycoprotein (dark green box), envelop (E) (dark blue box), membrane (M) (orange box), and nucleocapsid (N) (yellow box) proteins, accessory proteins such as orf 3a/b (red boxes), 5 (black box), 6 (pink box), 7a/b, 8a/b, 9b and 10 (red boxes), and the 3′-untranslated region (3′-UTR). The doted red lines (both in above and under) are the protein which show key differences among SARS-CoV-2, SARS-CoV and MERS-CoV. The nsps and orfs lengths are not drawn in scale (adapted from Islam et al. 2020; Shereen et al. 2020).

Figure 2. Phylogenetic tree of SARS-CoV-2.

200 complete genome sequences of SARS-CoV-2 retrieved from global initiative on sharing all influenza data (GISAID) (https://www.gisaid.org/) from different countries were used to build this tree. The sequences were aligned using MAFFT online server (Katoh, Rozewicki & Yamada, 2019), and a maximum likelihood tree was built with iTOL (interactive Tree Of Life). Each node represents a single strain which is found to be patient and/or sample specific, and not clustered according to geographical locations. Tree scale 0.01, represents days before the time of lastly sampled genomes by scale*365.

Figure 3. The dynamic curve showing daily increase in complete genome sequences of SARS-CoV-2 strain (s) from different patients across the globe, and being submitted to the reference databases.

The data were collected from China National Center for Bioinformation 2019 Novel Coronavirus Resource (2019nCoVR) with available sequences from different countries (as on May 7, 2020).