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Sars-Cov-2 is a virus that is particularly susceptible to mutation, as shown by the constant emergence of new variants. It also defends itself against possible drugs with modifications, as a case from the USA shows.
The German therapy guideline for Covid-19 also mentions Remdesivir. But doctors may not be able to rely on this drug for much longer. In a study, it was observed that Sars-CoV-2 could develop resistance to antiviral.
Paxlovid has shown high efficacy against severe covid-19 in trials. Nevertheless, it is not seen as a gamechanger in the pandemic.
Covid drug paxlovid is only a “stopgap” measure.
In the journal “Nature Communications,“ US physicians present the case of an immunocompromised lymphoma patient in whom a ten-day treatment with remdesivir was unsuccessful. The scientists suspect that a mutation in the virus made the drug ineffective. At the same time, the mutation also weakened the virus.
The possibility that Sars-CoV-2 could escape the reach of drugs through mutations had already been predicted in laboratory studies. Virologists have shown that the mutation E802 in the gene NSP12 alters the RNA-dependent RNA polymerase so that Remdesivir can slightly inhibit it.
Infectiologists discovered this mutation at Yale University School of Medicine in New Haven/Connecticut in a 70-year-old patient with non-Hodgkin’s lymphoma. After being treated with the antibody rituximab, the woman could not develop an antibody response against Sars-CoV-2. When she became infected with the coronavirus in May 2020 and contracted Covid-19, she developed a chronic infection. After 148 days of persistent infection, doctors decided to treat her with Remdesivir, which was extended from five to ten days out of concern for a relapse.
As Shiv Gandhi and his team report, the treatment was initially successful. A rising Ct value in the PCR test indicated a falling viral load. However, a relapse occurred while the patient was still being treated with Remdesivir. The doctors finally managed to end the infection by infusing the monoclonal antibodies basiliximab and imdevimab. These drugs were still effective against the variant circulating at the time.
The researchers examined several nasal, throat, saliva, stool, and blood samples taken during the disease. The genome of Sars-CoV-2 has been sequenced a total of 27 times. The E802 mutation was first discovered on the seventh day of remdesivir treatment. After a few days, it had prevailed over other variants. Tests confirmed that the mutation significantly weakened the effectiveness of remdesivir. Gandhi, the lead author of the study, suspects that immunocompromised patients may be more susceptible to developing resistance, “whether to a small molecule like remdesivir or antibody therapy.“
At the same time, the mutation reduced the infectivity of the viruses. According to the researchers, under normal circumstances, the mutant would probably not be able to establish itself. If Remdesivir prevents the multiplication of other variants, mutants with E802 have a chance.
Therefore, the researchers recommend a combination therapy, which successfully limited treatment resistance in the immunocompromised patient in the study. The scientists said it reduces the risk of a virus becoming resistant to a single therapy in a university statement. These treatments, which use multiple agents targeting different parts of a virus, have already successfully treated patients with HIV.
- source: ntv.de/picture:pixabay.com
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