Abstract
In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the direct action of AMPs. In a scenario where most host cell membranes are dressed by a pathogenic lipid composition, AMPs can indiscriminately attack them. This is why we use the “AMP betrayal” term to describe this mechanism. Previously proposed cytokine/bradykinin storm mechanisms are not incompatible with this new proposal. Interestingly, the harmful action of AMPs could be prevented by new therapies aimed to reestablish the lipid composition or to inhibit the action of specific peptides.
Highlights
Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus responsible for the coronavirus disease 2019 (COVID-19) global pandemic
The original contributions presented in the study are included in the article; further inquiries can be directed to the corresponding authors
The manuscript was written through contributions of all authors
Summary
Severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is a single-stranded positive-sense RNA virus responsible for the coronavirus disease 2019 (COVID-19) global pandemic. We hypothesize that the dramatic lipid alteration of the host cells caused by the virus could trigger the response of natural AMPs, activating the first line of defense toward host cells that should not be destroyed This assumption brings a new player, natural AMPs, into the overreactive innate immune response observed in COVID-19, resulting in destructive inflammation. The great influence that the composition of the lipid membranes has on the mode of action of natural AMPs is known, the lipid alteration that takes place in the host cells during COVID-19 has not been related to the action of these natural host defense peptides The scope of this assumption goes beyond the infection by SARS-CoV-2 and makes sense for other diseases. Some of these molecules could be taken as a reference to develop new drugs
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