New device empowers study of SARS-CoV-2 mutant range by ultrasequencing

Overview

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• Source: University of Malaga


• Date: 15 Feb,2021

SARS-CoV-2 genome is three times larger than flu genome. Both consist of NRA molecules which mutate when replicate. It is essential to know its mutant spectrum, in other words, its”fingerprints”, to achieve an appropriate treatment that reduces its infectivity -the capacity of pathogens to invade organisms and cause infections-, since its composition of variables could determine how infection would develop in each individual patient.

Researchers at the University of Malaga (UMA) will have the ability to inspect the depth of these spectra by hereditary ultrasequencing techniques as a result of the innovative system they’ve designed:”QuasiFlow”, a tool which permits the analysis of variants present in each patient individually.

“We’re interested in reaching a deep comprehension of the genetic variability of the virus to find out the best way to attack, its weak spot”, explains Professor Ana Grande from the Department of Cellular Biology, Genetics and Physiology of the UMA, who will lead a research next year, funded by the Government of Andalusia, to step up research into new rapid implementation therapies for COVID-19.

New antiviral therapy
Particularly, this researcher of the UMA will coordinate a multidisciplinary team of scientists who will test a new combination antiviral therapy, which combines the so-called lethal mutagenesis strategy and inhibitors of the ExoN proofreading and MTase activities of coronavirus, to be able to stop the virus from evading the innate immune response.

“The idea is to increase the mutation capacity of the virus to turn it against the virus, change its mutant spectrum so that it loses its infectivity”, says Ana Grande, who asserts that she has already achieved this on other RNA viruses, such as the lymphocytic choriomeningitis arenavirus or the hepatitis C virus, by employing nucleoside or base analogues, similar to the basic pieces which genomes comprise of.

The expert clarifies thatthis time, they will combine it with peptides -molecules comprised of a couple of amino acids-, specifically designed against its”Achilles heel”, the enzyme that corrects the mistakes that can wipe it out, to make lethal mutagenesis more effective and obtain better results.

The scientist of the UMA, who has been studying this sort of therapies on animal and plant viruses since 1999, guarantees that SARS-CoV-2 isn’t an exception, and that it is already proven that it is sensitive to these mutagenesis remedies.

Phases of study
They’ll analyze viral samples obtained from patients with different clinical circumstances, from asymptomatic to severe cases, including reinfected patients, in order to find clear differences in their spectra.

This first stage is conducted by the researchers and bioinformatics scientists of the UMA Gonzalo Claros, Enrique Viguera, Pedro Seoane, Luis Díaz, Josefa Gómez y Diego Lozano, in Addition to the specialists of Virgen de la Victoria University Hospital of Malaga Jesús Santos and Isabel Viciana.

After ultrasequencing and analyzing the mutant spectra, Ugo Bastolla, researcher of the Centre for Molecular Biology”Severo Ochoa” (CBM) of the Spanish National Research Council (CSIC), will carry out the modeling phase to identify the best analogue to perform the mutagenesis. Ana María Fernández and Gregorio Fernández, specialists in protein structures of Miguel Hernández University of Elche, will be in charge of designing the peptides.

“These scientists will design a tailored therapy based on the previous sequencing of the virus”, explains the research workers of the UMA, who adds that this realization is essential to accomplish new treatments to fight COVID-19, that different approaches should be studied because”we cannot risk everything on one throw” with this virus.

The trial on host cells to check the efficacy of the combination of these two therapies constitutes the final phase of the analysis. Researchers will have one year to conduct the trial and EUR 94,800 in the COVID-19 Fund of the Government of Andalusia, to be charged to the ERDF fund.