A decoy for covid
Defective viral particles reduce the transmission of coronavirus
Irina Konova, PCR.news
Scientists from the USA have developed mRNA-based particles that prevent the replication of SARS-CoV-2 in the body and alleviate the symptoms of infection. These particle properties have been confirmed on Syrian hamsters. In the new work, the authors showed that the particles also reduce the transmission of the virus.
When creating therapeutic particles, scientists were inspired by the so-called defective interfering particles (DIPs). DIPs are mutant viral particles incapable of self—replication. They parasitize normal viral particles, recruiting their replication tools, which leads to a decrease in the number of new functional particles leaving the infected cell. DIPs are described for many RNA viruses, including coronaviruses and influenza viruses. Initially, they were perceived only as artifacts of cultivation, but in the last ten years, scientists have begun to consider them as the basis for antiviral drugs.
The authors of the new work constructed engineering DIPs and called them therapeutic interfering particles — therapeutic interfering particle, or TIP. TIP consists of a non-coding part of the SARS-CoV-2 genome. They cannot replicate on their own, but they replicate together with functional viral particles in the same cell. Their main difference from DIP is the value of the base reproductive number R0. For therapeutic effect, it is necessary that R0 be greater than 1. Scientists have achieved this by genetic engineering methods.
At the end of 2021, they published an article describing antitussive TIP and the results of their testing in vitro and on hamsters. TIP did not cause an antiviral immune response, while inhibiting the replication of SARS-CoV-2 in lung organoids. With a single intranasal injection to infected hamsters, TIP also suppressed the reproduction of the virus, reduced inflammation and prevented pulmonary edema.
In the new work, the team tested whether engineered particles can restrain the transmission of the virus. They infected a group of ten hamsters with the delta SARS-CoV-2 strain. Six hours after infection, five hamsters were injected with TIP in the form of lipid nanoparticles, the remaining five received control nanoparticles without TIP. 36 hours after infection, that is, during the peak of contagion, a healthy hamster was planted to each sick hamster, and after another eight hours the hamsters were seated and monitored for several days.
TIP significantly reduced the viral load in the lungs of hamsters — sources of infection. Lung damage in hamsters who received TIP was not as extensive as in hamsters from the control group. Similarly, the hamsters who came into contact with the source from the TIP group had less lung damage than the contacts of the control group. According to the authors, this suggests a less intensive isolation of the infectious virus by hamsters from the TIP group. At the same time, the TIP itself was not transmitted to contact hamsters, which was confirmed by PCR analysis.
In additional experiments and using mathematical modeling, scientists have confirmed that a single injection of TIP reduces both the duration of the release of infectious SARS-CoV-2 and the amount of virus released. At the same time, TIP worked equally well against the delta strain and against the original Wuhan strain.
The team has now applied to the FDA for approval of the TIP clinical trials.
Chaturvedi et al. A single-administration therapeutic interfering particle reduces SARS-CoV-2 viral shedding and pathogenesis in hamsters is published in the journal PNAS.
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