Determining drug activity against SARS-CoV-2 using lab-generated lentiviral vectors pseudo-typed with the SARS-CoV-2 spike glycoprotein


C Patel1; A Lister1; A Evans1; L Oldfield1; K Roper1; J Thomas1; A Owen1; G Pollakis1; B Paxton1; A Plagge1; C Goldring1; E Costello1
1 University of Liverpool, UK


Introduction: The rapid spread and severity of the SARS-CoV-2 virus requires effective treatment strategies. With the emergence of SARS-CoV-2 variants, alternative therapies to vaccines such as pharmacotherapy could prove important. The SARS-CoV-2 spike glycoprotein mediates virus entry into target cells by binding to angiotensin converting enzyme 2 (ACE-2) receptor protein. By understanding and inhibiting the interaction between SARS-CoV-2 spike glycoprotein and ACE-2 receptor, SARS-CoV-2 could be prevented from entering host cells, thus averting the spread and infection within the population. As a safer, reproduceable and practical alternative for studying SARS-CoV-2 activity outside of biosafety level 3 containment, this study used variants of SARS-CoV-2 spike glycoprotein, pseudo-typed onto replication incompetent lentiviral vectors.

Aims: To generate a plasmid expressing the SARS-CoV-2 spike glycoprotein. To generate lentiviral vectors pseudo-typed with the SARS-CoV-2 spike glycoprotein. To assess the effects of drugs on the infectivity of SARS-CoV-2 pseudo-typed lentiviral vectors in a drug treatment assay. Methods: The pseudo-SARS-CoV-2 plasmid was generated by placing a FLAG-tagged SARS-CoV-2 gene under the control of a CMV promoter. Generated lentiviral particles were analysed for reporter activity by undertaking luminescence-based and viability assays. Dexamethasone and heparin were assessed for their ability to impede potential viral entry through interruption of the SARS-CoV-2 spike glycoprotein mediated viral entry process.

Results/Conclusion: SARS-CoV-2 spike glycoprotein lentiviral pseudo-typing system was developed and used to assess the inhibition of heparin and dexamethasone on viral entry. In the future, the system could be used to screen drugs that can inhibit the interaction of SARS-Cov-2 spike glycoprotein and variants (N429K, Y453F and N439K del 69-70) with its receptor.

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