Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses

Authors: Xi Yu et al.

Link to paper: https://doi.org/10.1101/2020.05.22.109900

Journal/ Pre-Print: bioRxiv

Tags Anti-viral treatment

Research Highlights 

1. Identification of two bacterial lipases, secreted by a Chromobacterium and named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, that have virucidal activity against multiple enveloped viruses including SARS-CoV-2.

2. CbAE-1 and CbAE-2 virucidal activity is mediated by their lipase activity against the viral envelope that causes the exposure of the viral mRNA.

3. CbAE-2 is less toxic than CbAE-1 for both human and mice cells.

Summary

This study identifies two secreted bacterial proteins from a chromobacterium, CbAE-1 and CbAE-2, with antiviral activity against several viruses, including SARS-CoV-2. The authors isolate these secreted proteins from the bacterial viral supernatant, identify them through mass spectrometry and confirm their identity as lipases. The antiviral activity of CbAE-1 and CbAE-2 is mediated by enzymatic degradation of the lipid viral envelope and it is blocked when CbAEs mutants, lacking the core motif for lipase activity, are employed. CbAE-2 is less toxic than CbAE-1 on both human and mice cells. CbAE-2 is better tolerated by mice when administered via intranasal inoculation than tail-vein injection. Both CbAE-1 and CbAE-2 do not have any effect on influenza A virus.

Impact for SARS-CoV2/COVID19 research efforts

Treat of SARS-CoV2/COVID19 positive individuals

Authors purpose that CbAEs could be used to treat SARS-CoV-2 patients. CbAEs exhibit cytotoxicity against human cells so their affinity and specificity would have to be improved. According to the authors, production of CbAEs engineered with ACE2 is plausible.

Study Type

· In vitro study

· In vivo study (8-week old ICR female mice)

Strengths and limitations of the paper

Novelty: Production of antiviral molecules by species within the genus Chromobacterium has been studied before (Andrighetti-Frohner 2003). Nevertheless, these CbAEs have never been identified before and they have never been tested on SARS-CoV-2.

Standing in the field: To our knowledge, this is the first paper that have been published on the antiviral activity of CbAEs agaist SARS-CoV-2.

Appropriate statistics:

No statistical approach was employed to decide the sample size for the experiments in vivo. All experiments in vitro were analysed using GraphPad Prism and data were confronted employing a student’s t-test.

Viral Model used: SARSCov-2 and SARS-CoV-2 pseudovirus that was purchased from GenScript.

Translatability: These CbAEs could be used as frontline drugs to treat SARS-CoV-2 when symptoms arise. Authors purpose that CbAEs could be engineered with ACE2 to increase their affinity and specificity for the viral envelope.

Main Limitations: Authors do not specify how many times they repeat each experiment and thus it is hard to know whether the results shown in the figures are representative. There is no attempt to explain why these CbAEs do not have any effect on influenza A virus. It would have been nice to see these CbAEs tested also on an animal model of the infection (the experiments in vivo are limited to a toxicological analysis).