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Snake Venom Shows In vitro Anti-SARS-CoV-2 Activity

Snake venom has been reported to contain compounds with many physiological activities. A new study explores one component of snake venom, the secreted phospholipase A2 enzymes (sPLA2s), which have a wide range of diverse sequences and biological functions. PLA2s are small secreted enzymes that facilitate the hydrolysis of membrane glycerophospholipids to lysophospholipids and free fatty acids.

An earlier study on dimeric PLA2 crotoxin, from Crotalus durissus terrificus, and its active subunit PLA2-CB, were able to inactivate dengue virus type 2, among other viruses, by splitting the glycerophospholipids of the virus envelope. The researchers found that sPLA2s act against SARS-CoV-2 in vitro, particularly group IIA dimeric PLA2s. When the virus was treated with the two dimeric PLA2s HDP-1 and HDP-2, strong virucidal activity was observed to result. The researchers also found that at concentrations varying between 1 to 100 μg/ml, both dimeric HDP-1 and HDP-2 inhibited spike-mediated syncytia formation, thus hindering the virus’s spread between cells. While there was about 70% inhibition at 100 μg/ml, it was reduced to about 48% at 1 μg/ml. Notably, the active subunit HDP-2P completely blocked the cell-cell fusion at 100 μg/ml. This could indicate that they can prevent viral entry into cells.

The anti-proliferative and cytotoxic effect of PLA2s reported in earlier studies is directed against cancer cells, mainly, and not normal cells. Moreover, the PLA2s studied here were used at very low concentrations, orders of magnitude lower than that required to produce an effect on normal cells. The researchers also found some degree of similarity between the S protein of SARS-CoV-2 and the dimeric PLA2s, especially the spike segment that interacts with the host cell ACE2 receptor. This may indicate that dimeric PLA2s competitively inhibits viral binding to ACE2.

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