Recent global health
concern motivated the exploration of natural
medicinal plant resources as an alternative target for treating COVID-19
infection and associated inflammation. In the current study, a phytochemical,
6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was
investigated as a potential anti-inflammatory and anti-COVID-19 agent.
In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2
replication. When tested in the inflammasome activation model, 6-SHO
displayed mechanistic action by regulating the expression of the inflammasome
pathway molecules. In comparison to the existing drugs, remdesivir
and hydroxy-chloroquine, 6-SHO was not only found to be as effective
as the standard anti-viral drugs but also much superior and safe in
terms of predicted physicochemical properties and clinical toxicity.
Comparative molecular dynamics simulation demonstrated a stable interaction
of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit
water environment. Overall, this study provides important cues for
further development of 6-SHO as potential anti-inflammatory and anti-viral
therapeutic agents.