Article ; Online: Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin.
2021 Volume 12, Issue 1, Page(s) 2946–2956
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 ... ...
| 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 24 h 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 72 hpi. 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. |
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| MeSH term(s) | Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Coinfection ; Humans ; Pandemics ; SARS-CoV-2/drug effects ; Thapsigargin/pharmacology ; Thapsigargin/therapeutic use ; COVID-19 Drug Treatment |
| Chemical Substances | Antiviral Agents ; Thapsigargin (67526-95-8) |
| Language | English |
| Publishing date | 2021-10-13 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2657572-3 |
| ISSN | 2150-5608 ; 2150-5594 |
| ISSN (online) | 2150-5608 |
| ISSN | 2150-5594 |
| DOI | 10.1080/21505594.2021.2006960 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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