Since the outbreak of the new disease caused by SARS-CoV-2 broke out in China, laboratories around the world have been working around the clock to develop tools that allow us to deal with the virus. It is a problem that can be approached from multiple approaches: rapid detection tests, drug and vaccine development, use of blood plasma from cured patients …
The amount of new information that emerges every day is absolutely overwhelming. A search of the Google Scholar scientific database returns a list of more than 1,650 articles, and dozens of new papers are added every day. How can both scientists and the general population assume such a huge amount of information?
In order to organize and sift through the available information, a team of researchers from the University of North Carolina at Chapel Hill has just published a review and assessment that compiles the most promising strategies to fight the most dangerous coronaviruses (not just SARS). -CoV-2 but also its relatives such as SARS and MERS), as well as the potential new coronaviruses that may cause pandemics in the future. The researchers propose that the most promising approach is the selection of antivirals and the use of gene therapy for rapid advancement.
“Coronaviruses pose a real threat to human health and the global economy,” explains Ralph Baric, one of the authors. “We must consider new countermeasures to control the SARS-CoV-2 pandemic virus, as well as the wide variety of zoonotic viruses that also pose a threat and may cause problems in the future.”
Vaccines
In the article, which is published in the journal Frontiers in Microbiology , the authors discuss one by one the possible ways to approach the fight against the coronavirus. The most effective would undoubtedly be the development of a vaccine. The results of all pre-clinical and clinical trials published so far on vaccines against SARS and MERS have also been included in this review.
As indicated a few days ago by the World Health Organization, there are currently at least seventy vaccines in development against the new coronavirus, and several of them are already being tested in humans. According to the current review, the most promising vaccine approaches are those that take advantage of the receptor-binding site – the so-called S protein of the virus – which allows it to bind and fuse with the cells it is about to infect.
The authors emphasize, however, that since the amino acid sequence of protein S is very different between different coronaviruses, vaccines that work against one strain will probably not be effective against others.
The work also highlights that, in addition to traditional vaccines that use live attenuated subunits of viruses, modern approaches based on DNA or RNA and nanoparticle vectors are also promising.
However, and since the development of a vaccine takes a long time (years, probably), it is necessary to address other approaches that allow a quick way out of the current global health emergency.
Antivirals
In the search for effective drugs against COVID-19, the most promising are broad-spectrum antivirals, such as nucleoside analogs. As their name indicates, these drugs mimic some of the nucleosides, which are the building blocks that make up the genetic material, DNA or RNA of viruses. By ‘sneaking’ into the nucleic acid chain, its synthesis is interrupted and the replication process of the virus stops.
The fundamental problem with this approach is that coronaviruses have an enzyme that is precisely responsible for correcting possible errors found during the replication of genetic material, and this limits the action of the aforementioned antivirals. For now, the exceptions seem to be two drugs: β-D-N4-hydroxycytidine and remdesivir, both proposed by the authors as good candidates against SARS-CoV-2.
Blood plasma from recovered patients
A quick fix to tackle the problem in developing the long-awaited vaccine or developing effective drugs is a technique already employed during the 1918 flu pandemic: the use of blood plasma from recovered patients. It would be about providing short-term passive immunity by taking advantage of the antibodies generated by people who have already had the disease.
One of the advantages of this technique is that only the equipment necessary for a normal blood transfusion is needed to carry it out, and although its effectiveness needs to be verified, it can be an express solution that saves lives and helps to avoid the increase in the number of serious cases that collapse the ICUs of hospitals.
Gene therapy
Another of the most attractive alternatives, according to the authors, to fight against COVID-19 in which a vaccine is developed would be gene therapy, which consists of the transfer of genetic material to cells or tissues of the patient through a vector, which in this case would be an adeno-associated virus (AVV).
This would involve the rapid and targeted delivery of antibodies, immunoadhesins, antiviral peptides, and immunomodulators to the upper airways, to provide short-term protection and with minimal toxicity risks. The authors estimate that these types of tools can be developed, adapted, and tested in as little as one month.
“Passive immunization based on AAV can be used as a rapid alternative. It is simple and contains only two components, the viral vector and the antibody,” explains Victor Longping, another of the authors. “In theory, a single dose could generate a protective response in a week and last more than a year. Perhaps it is too late to treat SARS-CoV-2, but it could in any case be taken into account for future outbreaks of the disease ”.
Referencia: Longping et al. 2020. The Current and Future State of Vaccines, Antivirals and Gene Therapies Against Emerging Coronaviruses. Front. Microbiol., 24 April 2020
