Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin

Al-Beltagi, Sarah; Goulding, Leah V.; Chang, Daniel K.E.; Mellits, Kenneth H.; Hayes, Christopher J.; Gershkovich, Pavel; Coleman, Christopher M.; Chang, Kin-Chow

Abstract

The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95% (relative to controls) at 72hpi. Likewise, TG was effective in inhibiting each variant in active preexisting infection. In conclusion, against the current backdrop of the dominant D variant that could be further complicated by co-infection synergy with new variants, the growing list of viruses susceptible to TG, a promising host-centric antiviral, now includes a spectrum of contemporary SARS-CoV-2 viruses.

Citation

Al-Beltagi, S., Goulding, L. V., Chang, D. K., Mellits, K. H., Hayes, C. J., Gershkovich, P., Coleman, C. M., & Chang, K.-C. (2021). Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin. Virulence, 12(1), 2946-2956. https://doi.org/10.1080/21505594.2021.2006960

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2021
• Online Publication Date: Dec 12, 2021
• Publication Date: Dec 31, 2021
• Deposit Date: Nov 18, 2021
• Publicly Available Date: Dec 12, 2021
• Journal: Virulence
• Print ISSN: 2150-5594
• Electronic ISSN: 2150-5608
• Publisher: Taylor and Francis
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• Pages: 2946-2956
• DOI: https://doi.org/10.1080/21505594.2021.2006960
• Keywords: Infectious Diseases; Microbiology (medical); Immunology; Microbiology; Parasitology
• Public URL: https://nottingham-repository.worktribe.com/output/6729999
• Publisher URL: https://www.tandfonline.com/doi/full/10.1080/21505594.2021.2006960