Evaluation of diversity levels in HIV-1 virus integrase gene sequences, supporting the lack of target specificity of ivermectin versus the integrase-importin complex in SARS-CoV-2 infection (Brazil, 2020-07-20, Preprint)

[-] TrumpLyftAlles | 1 points | Jul 21 2020 17:10:32

There's a 14-page PDF available on the linked page.

Abstract

Therapies with new drugs have been appearing in tests worldwide as potential inhibitors of sars-cov-2 virus replication. Recently, one of these drugs, Ivermectin, was reported as an inhibitor of the nuclear import of HIV-1 proteins in vitro, soon becoming the target of an international prospecting work (not yet published), with patients tested for COVID-19.

However, understanding the evolutionary aspects of the biological components involved in the complex drug-nuclear import helps in understanding how these relationships exist in the deactivation of viral infections. Thus, 153 sequences of the HIV-1 integrase gene were analyzed for their genetic structure and molecular diversity and the presence of two distinct groups for the Gene and not only one, was detected; As well as different degrees of structuring for each of these groups.

These results support the interpretation of the lack of conservation of the HIV-1 gene and that the number of existing polymorphisms, only for this structure of the complex, implies the non-efficiency of a drug at population levels. Thus, the molecular diversity found in HIV-1 can be extrapolated to other viruses, such as Including, sars-cov-2 and the functionality of the drug, interacting with the integrase-importin complex, can be further decreased.

The site of ivermectin's action has variation in HIV-1 populations; this implies it won't work for everyone, if the covid-19 virus shows similar variation. (???)

This is the conclusion from the PDF:

This consideration provides certainty that an efficient response of drugs that destabilize the integrase-importin link such as ivermectin should not be expected for all HIV1 viruses from humans, whether they come from the same geographic region (as this study shows), or even more from samples from geographically distinct regions and thus, by extrapolating the levels of polymorphism and molecular diversity found in the samples of this study, for other RNA viruses, such as Sars-Cov-2, the integrase-importin relationship may be even more diverse, and may bring less and less functionality to drugs that interact with it in the role of destabilizing the integrase-importin complex, which in turn inhibit or reduce the infectious potential of any RNA virus.

I read that as "Genetic variation observed with HIV1 viruses suggest that ivermectin's action via the IMP alpha/beta1 proteins may be limited by genetic diversity."