Emergence and Reemergence of Human Coronaviruses: Spike Protein as the Potential Molecular Switch and Pharmaceutical Target

(E-pub Ahead of Print)

Author(s): Fahim Ahmad*, Mohammad A. Kamal, Babu L. Tekwani*

Journal Name: Current Pharmaceutical Design


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Abstract:

Background: Recent emergence of COVID-19 caused by a new human coronavirus (CoV) strain (SARS-CoV2), which originated from the China, poses future emergence of additional CoVs. In most of the cases of emergence of human CoVs bats, palm civets, raccoon dogs and camels have been identified as the sources of human infections and reservoir hosts. A review of comparative genomic and phenotypic characteristics of human CoV strains vis-à-vis their comparison with the corresponding animal isolates shall provide the clues regarding the potential genomic, phenotypic and molecular factors responsible for host-switching, which may lead to prospective emergence and reemergence of human CoV outbreaks in future.

Methods: The seven known human strains of CoV were analyzed for the host and viral factors responsible for human outbreaks. The molecular factors responsible for host-susceptibility, virulence and pathogenesis were reviewed to predict emergence and re-emergence of additional human CoV strains. CoV spike protein was evaluated as a potential viral receptor for host switching and the target for pharmaceutical design.

Results: Review of the factors associated with host-susceptibility, virulence and pathogenesis of seven known human CoV strains present significant possibilities for emergence of new CoV strain(s), leading to more human outbreaks. Continuous exposure of animals’ handlers to the infected animals, environmental changes, improper sanitations, nondisposal of the solid waste and resumption of exotic animals markets provide favorable conditions for “host switching” and emergence of new and potentially more virulent human CoV strains. Mutations in target genes (like spike protein), which facilitate the viral entry into the host-cells, provide potential “molecular switch” for preferences of new hostreceptors, genetic diversity, genetic-recombination and high virulence. Additionally, the clinical and environmental factors, asymptomatic carriers, paucity of efficacious vaccines & therapeutics, inefficient disease management and infection control measures, lack of public awareness, and effective communication of information about more virulent human-adapted virus isolates are critical factors for emergence of new and virulent SARS-CoV strains with high mortality and varied incubation period in the near future. Small molecules binding with conserved druggable regions of the CoV spike proteins may be effective against multiple strains of CoVs.

Conclusions: High propensity of mutations and “molecular adaptations” in coronaviruses create the hot spots and high potential for “host switching” leading to emergence of more virulent strains human CoVs. The public/global health agencies, medical communities and research scientists should be prepared for emergence and reemergence of new human CoV strain(s) leading to potential disease outbreaks. The inhibitors binding with conserved druggable regions of spike proteins from multiple strains CoV may have utility as broad-spectrum antiviral drugs to combat future emergence of CoVs.

Keywords: Coronaviruses, COVID-19, spike protein, SARS-CoV-2, SARS-CoV, MERS-CoV, emerging infectious diseases, antiviral drugs, viral host-switching, public health, global health, antiviral targets.

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1381612826666201216113146
Price: $95

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