Midway through the pandemic outbreak, investigators attempts to highlight some of the strongest candidates to fight the disease.
As the coronavirus disease 2019 (COVID-19) pandemic sparks hundreds of new scientific papers outlining disease pathology, possible therapies, and vaccine candidates, a new review article aimed to highlight some of the strongest strategies for fighting the pandemic.
Writing in Frontiers in Microbiology, corresponding author Ralph S. Baric, PhD, of the University of North Carolina, Chapel Hill, and colleagues distilled clinical information about SARS-CoV-2 as well as the viruses that cause severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), as well as potential future strains.
Baric said gene therapies and antivirals like remdesivir seem to be the most promising treatments thus far for the current pandemic.
“Coronaviruses represent a true threat to human health and the global economy,” he said in a statement. “We must first consider novel countermeasures to control the SARS-CoV-2 pandemic virus and then the vast array of high-threat zoonotic diseases that are poised for human emergence in the future.”
Baric and colleagues said the most important and urgent strategies against SARS-CoV-2 is a vaccine, with both existing and novel strategies needing to be used to try and find the optimal vaccine candidate. The team wrote that vaccines that target the receptor binding domain of the virus’s S-protein are most likely to be successful at neutralizing the virus.
DNA and RNA vaccines should be considered, investigators noted, as should nanoparticle- or viral vector-borne vaccines. Efforts should also continue to find a vaccine using more traditional methods, such as vaccines that leverage live-attenuated or inactivated virus, and subunit-based vaccines.
In the meantime, broad-spectrum antivirals like nucleoside analogs are likely a meaningful method to curb the virus, the team wrote. These therapies work by mimicking the bases in the virus’s RNA genome, thereby being incorporated into RNA chains and stalling the virus’s copying mechanism.
The problem, though, is that coronaviruses are efficient at identifying and removing these mismatches, rendering most nucleoside analogs ineffective. However, β-D-N4-hydroxycytidine and remdesivir seem to be exceptions.
Another therapeutic option that has been researched and which the authors said might be effective is plasma-based therapy. These therapies are mass-produced based on antibodies or monoclonal antibodies isolated from patients who have recovered from COVID-19 infections. Such interventions can result in short-term immunity.
Baric and colleagues wrote one of the most promising potential therapies, however, is gene therapy using adeno-associated virus (AAV). In the therapy, antibodies, immunoadhesins, antiviral peptides, and immunomodulators are delivered in a targeted fashion to the upper airways of a patient. The process confers short-term protection with minimal risk of toxicity.
“AAV-based passive immunization can be used as a quick alternative,” said co-author Long Ping Victor Tse, PhD. “It is straightforward and only contains two components, the viral vector and the antibody. Multiple AAV vectors have been proven to be safe and effective for human use.”
The authors also discussed a number of other potential strategies for dealing with COVID-19, but concluded by arguing that given the significant amount of research already being conducted, there is strong reason to believe the pandemic can be stopped.
“The current SARS-CoV-2 poses a huge challenge for society; however, given experience with emerging CoVs and global effort, it is hoped that the impact of the outbreak will be minimal,” they wrote.