Insights into the evolutionary and prophylactic analysis of SARS-CoV-2: A review

Abstract

In late 2019, following the emergence of a β-originated SARS-CoV-2, phylogenetic and evolutionary approaches have been demonstrated to strengthen the diagnostic and prophylactic stratagem of COVID-19 at an unprecedented level. Despite its clinical prominence, the SARS-CoV-2 gene set remains largely irrefutable by impeding the dissection of COVID-19 biology. However, many pieces of molecular and serological evidence have predicted that SARS-CoV-2 related viruses carry their roots from bats and pangolins of South East Asia. Analysis of viral genome predicts that point mutations at a rate of 10^-4 nucleotides per base in the receptor-binding domain allow the emergence of new SARS-CoV-2 genomic variants at regular intervals. Research in the evolution of molecular pathways involved in emergence of pandemic is critical for the development of therapeutics and vaccines as well as the prevention of future zoonosis. By determining the phyletic lineages of the SARS-CoV-2 genomic variants and those of the conserved regions in the accessory and spike proteins of all the SARS-related coronaviruses, a universal vaccine against all human coronaviruses could be formulated which would revolutionize the field of medicine. This review highlighted the current development and future prospects of antiviral drugs, inhibitors, mesenchymal stem cells, passive immunization, targeted immune therapy and CRISPR-Cas-based prophylactic and therapeutic strategies against SARS-CoV-2. However, further investigations on Covid-19 pathogenesis is required for the successful fabrication of successful antivirals.

Keywords: Antiviral drugs; CRISPR-Cas; Phylogenetic lineage; SARS-CoV-2 variants; Vaccines.

Graphical abstract

Fig. 1

Schematic representation of SARS-CoV-2 genomic organization, canonical sub genomic mRNAs in grey color and the virion structure (modified from Kim et al., 2020).

Fig. 2

The evolutionary history of Surface glycoprotein of SARS-CoV-2 from USA, Iran, Taiwan, New Zealand, Peru, Egypt, Pakistan, Ghana, Libya, Australia, United Kingdom, China, Thailand, Japan, Hong Kong, Brazil, India was inferred by using the Maximum Likelihood method and General Time Reversible model. The bootstrap consensus tree inferred from 500 replicates is taken to represent the evolutionary history of the taxa analyzed. Branches corresponding to partitions reproduced in less than 50 % bootstrap replicates are collapsed. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. Initial tree(s) for the heuristic search were obtained automatically by applying Neighbor-Join and BioNJ algorithms to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach, and then selecting the topology with superior log likelihood value. This analysis involved 24 nucleotide sequences. Evolutionary analyses were conducted in MEGA X.

Fig. 3

A schematic representation of and immune response of patient to SARS-CoV-2. (A) Through fecal contamination and respiratory droplets of infected person, virus is targeting lungs of other healthy person. After the entry of virus inside the alveoli of lungs, macrophages get activated to release cytokines i.e. IL1, IL6 and TNF-α. The produced cytokines will start to infiltrate into the pulmonary capillary surrounding the alveoli. From there, by increase in permeability and vasodilation of blood capillary, cytokines will influence Nervous system, Circulatory system and Respiratory system. By affecting hypothalamus of brain, the condition of pyrexia or fever may prevail and by affecting circulatory system, the problem of Multi system organ failure may appear. Critically ill COVID-19 patients certainly meets clinical Systemic inflammatory response syndrome (SIRS) criteria that is further supported by markedly elevated levels of pro-inflammatory cytokines. However, after attacking the chemoreceptors in sympathetic nervous system, respiratory rate of patient may increase drastically. Due to the infiltration of cytokines, the phenomenon of alveolar edema may increase breathing rate and the patient face the problem of asthma too. (B) After using ACE2 receptor to get entry inside the host and utilizing RNA dependent RNA polymerase, the inserted RNA make multiple copies of viral genome and the produced viral proteins will assemble to give rise new viral particles. ⁽ⁱ⁾ SIRS = Systemic inflammatory response Syndrome. ⁽ⁱⁱ⁾ PO₂ = Partial Pressure of Oxygen. ⁽ⁱⁱⁱ⁾ SNS = Sympathetic nervous system. ^(iv) RDRP = RNA dependent RNA polymerase.

Fig. 4

Schematic representation for prophylactic approaches for COVID-19. (1) The production of universal vaccine incorporates the concept of immunity from all strains of coronaviruses and the reported vaccine formulations involve Protein subunit vaccine, Viral vectored vaccine, RNA based vaccine and DNA based vaccines that involves Antigen presenting cells and the immune reponse in the form of antibodies after certain dosage to the cell. (2) Formation of monoclonal antibodies involve the hybridoma technique to treat the malady of COVID-19. (3), (4) ACE2 receptor blockers and Fusion inhibitors impede the entry of virus inside the host cell. (5) Various antiviral drugs and endocytic blockers like Darunavir that inhibits the priming of SARS-CoV-2, hydroxyl-chloroquine and various endocytic pathway blockers that inhibits the endocytosis of virus, remdesivir inhibits the activity of RdRp thus inhibiting the replication of viral genome. (6) Mesenchymal stem cells produce anti-inflammatory cytokines impede the inflammation caused by viral infections.