Study claims drug target site found in spike protein of SARS
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A group of researchers at the University of Bristol, UK claim that the spike protein of the COVID-19 causing virus has a druggable site that, if successfully targeted, can keep the virus from infecting host cells, according to the study published in the peer-reviewed journal Science.

Key findings:

SARS-CoV-2 virus uses a trimeric spike protein to bind to ACE2 receptors on host cells and enter into target cells.

Research team isolated copies of the SARS-CoV-2 spike protein in lab culture and then made a 3D structure of this protein.

Found both closed and open confirmation spike proteins in the isolated sample, with about 70% being closed structures.

A small molecule called linoleic acid (LA) was found buried inside the spike protein in the ones with closed conformation.

Linoleic acid is important part of cell membranes and provides fluidity to the water barrier in the epidermis. In the outer membrane of lung cells, LA helps us breathe properly. On the flip side, LA is also associated with conditions like inflammation and cancer.

Previously, open S protein structures have been more common. This brings in the possibility that LA somehow stabilised the closed S configuration and may hence be used to target SARS-CoV-2.

LA causes changes in the receptor binding trimer and may be used to prevent the SARS-CoV-2 binding with ACE-2 and, in turn, the infection.

To study the effects of the site the researchers added 50-100 µM LA along with various doses of remdesivir to the virus-infected cells in a lab culture.

It was found that LA supplementation reduces the levels of remdesivir needed to fight the virus.

“Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic” said author.

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