New device enables study of SARS-CoV-2 mutant spectrum by ultrasequencing

The SARS-CoV-2 genome is three times larger than the influenza genome. Both contain NRA molecules that rotate when reproduced. Knowing its mutant spectrum, in other words, its “fingerprints”, is essential to achieve appropriate treatment that reduces its infectivity – the ability of pathogens to attack organisms and cause diseases -, for its changes could make a difference as would disease. improvement in all patients.

Researchers at the University of Malaga (UMA) will be able to study the depth of these spectra with genetic ultrasequencing techniques thanks to their innovative system design: “QuasiFlow”, a tool that enables the analysis of variables present in each individual patient.

“We are interested in reaching a deep understanding of the genetic variability of the virus in order to determine the best way to attack, rather than its weak spot”, explains Professor Ana Grande from the Department of Biology. Cellular, Genetics and Psychology of the UMA, which will lead next year’s study, funded by the Government of Andalusia, to phase out a study of new rapid-acting therapies for COVID-19.

New antiviral therapy

In particular, this researcher of the UMA will coordinate a multidisciplinary team of scientists who will test a new antiviral hybrid, which combines a so-called lethal mutagenesis strategy and -block ExoN detection activity and MTase activities of coronavirus, to prevent the virus. from avoiding a textured immune response.

“The idea is to increase the mutated ability of the virus to turn against the virus, changing its mutant spectrum so that it loses its infectivity,” says Ana Grande, who says it has achieved i this about other RNA viruses, such as the lymphocytic arenavirus choriomeningitis or the hepatitis C virus, using nucleoside or base analogues, similar to the basic fragments in which genomes are made up.

The expert clarifies that, this time, they combine it with peptides -molecules made up of a number of amino acids-, designed specifically against its “Achilles heel”, the enzyme that corrects errors that can be eliminated, to make lethal mutagenesis more effective and get better results.

The UMA scientist, who has been studying these types of treatments for animal and plant viruses since 1999, confirms that SARS-CoV-2 is no exception, and has already been proven to is aware of these mutagenesis therapies.

Research standards

In this way, in the first phase, which has already begun, researchers will apply the UMA software “QuasiFlow” to study the mutant spectrum of samples from the Virgen de la Victoria University Hospital in Malaga. They analyze viral samples obtained from patients with a variety of clinical cases, from asymptomatic cases to severe cases, including patients with relapses, to detect clear differences in their spectacles.

This first phase is led by UMA bioinformatics researchers and scientists Gonzalo Claros, Enrique Viguera, Pedro Seoane, Luis Díaz, Josefa Gómez y Diego Lozano, as well as Virgen de la Victoria University Hospital experts in Malaga Jesús Santos and Isabel Viciana.

After ultrasequencing and analysis of the mutant spectra, Ugo Bastolla, a researcher of the Center for Molecular Biology “Severo Ochoa” (CBM) of the Spanish National Research Council (CSIC), conducts the modeling stage to identify the best analogue to achieve the mutagenesis. Ana María Fernández and Gregorio Fernández, experts in protein structures at Miguel Hernández University in Elche, will lead the design of the peptides.

“These experts will design a specific treatment based on the previous strain of the virus”, clarifies the UMA researcher, who says that this performance is necessary to achieve new treatments to fight COVID- 19, that different strategies should be studied because “we can’t compromise everything with one throw” with this virus.

The experiment on host cells to test the efficacy of a combination of these two therapies makes up the final phase of the study. Researchers will have one year to make the case and EUR 94,800 from the Andalusian Government’s COVID-19 Fund, payable to the ERDF fund.