How to treat COVID-19?
In an unprecedented effort, hundreds of thousands of researchers and clinicians around the world are engaged in a race against time to develop drugs, vaccines and diagnostic tests for COVID-19, the disease that causes the SARS-CoV-2 virus.
More than 1,650 articles about COVID-19 have already been published in such large databases as Google Scholar, and dozens are added daily. In the registry ClinicalTrials.gov more than 460 clinical trials of COVID-19 have been registered – however, most of them are at the earliest stages. Given the variety of experimental approaches in these studies, there is a need to systematize possible clinical strategies.
In a new study published in the journal Frontiers in Microbiology, experts from the University of North Carolina at Chapel Hill examined possible strategies to combat dangerous coronaviruses, both SARS-CoV-2 and related viruses (SARS-Cov, which causes severe acute respiratory syndrome, and MERS-Cov, which causes Middle East respiratory syndrome)., as well as as yet unknown strains that will inevitably appear in the future.
The most promising approaches, according to researchers, are antiviral drugs (remdesivir, etc.) and gene therapy.
The authors presented possible strategies to combat coronavirus. The first and most effective are vaccines.
In this case, the most successful vaccines are those carrying the Receptor Binding Domain, which neutralizes the viral S-protein and does not allow it to bind to host cells. In addition to traditional live attenuated (attenuated), inactivated and subunit vaccines, modern types of vaccines based on DNA, RNA and nanoparticles or viral vectors should be considered.
Since the amino acid sequence of the S-protein is very different among different coronaviruses (for example, the similarity between SARS-Cov and SARS-Cov-2 is 76-78%), vaccines against one strain usually do not work against the other.
The development and testing of new vaccines takes from one year to several years, so it is necessary to develop other methods of control.
The second most likely effective approach is broad-spectrum antiviral drugs, in particular, nucleoside analogues that mimic the bases in the RNA of the virus, are incorporated into new RNA chains and stop the copying process.
But since coronaviruses contain a so-called correcting enzyme that can eliminate such errors, most nucleoside analogues do not work. The exceptions seem to be β-D-N4-hydroxycytidine and remdesivir, proposed by the authors as effective candidates for combating SARS-Cov-2.
The third approach is to inject blood plasma from recovered patients. It contains a low level of a number of antibodies against the virus. Monoclonal antibodies isolated and mass-produced with the help of biotechnologies are more effective (but slower to be produced). Such passive immunization will help to create short-term immunity.
The authors of the article discuss a number of other options, from fusion inhibitors to protease inhibitors, immunomodulators and others.
Finally, from the researchers' point of view, the most attractive alternative until a vaccine is produced is gene therapy carried out through an adeno-associated virus (AAV). It will provide rapid targeted delivery of antibodies, immunoadhesins, antiviral peptides and immunomodulators to the upper respiratory tract to provide short-term protection. Since there is a rapid turnover of cells in the respiratory tract, the risks of toxic effects are minimal. According to the authors, such tools can be developed, adapted and tested within a month. Passive immunization based on AAV is quite simple and includes only two components: a viral vector and an antibody. It has been proven that multiple AAV vectors are safe and effective for human use.
Theoretically, one dose can cause a protective reaction for a week and act for more than a year. Currently, the high price can be reduced in the treatment of infectious diseases due to the large market.
It may be too late to use AAV to treat SARS-CoV-2, but they will certainly be useful in future outbreaks.
Article by L.V.Tse et al. The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses is published in the journal Frontiers in Microbiology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Frontiers Science News: The most promising strategies for defeating coronavirus: a review study.