For the past several weeks, we’ve been focusing on explaining the science behind vaccines, explaining the different types of vaccines that are in development to prevent Covid-19, the disease caused by the novel coronavirus Sars-Cov-2. This week, guest author Kevin Curran explains the science behind some of the antivirals being tested for COVID-19.
As COVID-19 works its way through the population, one of the brightest lights on this bleak horizon is the possibility of a safe and effective pharmaceutical intervention. Biopharma companies are hard at work designing and testing different antiviral drugs. If all goes well, a few of these drugs will work, and Sars-Cov-2 will be brought to its knees.
Term of the Week: Antivirals
Antivirals are small drugs that disrupt some specific step of the virus life cycle.
The list below highlights critical life cycle steps for any virus:
- Attachment to a host cell.
- Release of viral genetic material into the host cell.
- Replication of viral components using the host cell’s machinery.
- Assembly of viral components into new viruses.
- New viruses release from host cell to infect new host cells.
The image below illustrates the SARS-CoV-2 life cycle in detail:
Benefit of applying a pre-existing antiviral to Covid-19
Developing a new drug and securing FDA approval typically takes about a decade. A quicker alternative? Re-purposing a drug that has already received FDA approval. There are already a number of effective drugs on the market for viral diseases such as HIV, Ebola, and influenza. Because these viruses have different structures than Sars-Cov-2, there’s no guarantee that drugs targeting steps of their life cycle will work against COVID-19. But testing them is worth a shot, and in a few cases preliminary data suggests some of these already-approved drugs may be useful. If a short, Phase III trial determines that one of these pre-existing antivirals is also effective at treating COVID-19, we may see these drugs distributed broadly as soon as early summer 2020.
In late March 2020, the World Health Organization launched a global clinical trial, Solidarity, to see how effective the four most promising COVID-19 treatments are. Thousands of patients will receive one of the following treatments: chloroquine and hydroxychloroquine, remdesivir, lopinavir and ritonavir, or a combination of lopinavir and ritonavir plus interferon-beta. Let’s take a look at how these promising antiviral drugs work. (Article continues below)
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Hydroxychloroquine (HCQ)
Chloroquine is an anti-malaria pill that’s been around since 1949. The FDA approved the drug after World War II.
In 2005, scientists reported that chloroquine was an effective antiviral against the original SARS coronavirus. These experiments were conducted on cells grown in a lab as opposed to cells in a living body.
Hydroxychloroquine (HCQ) is an analogue of chloroquine, which is thought to have a better safety profile than chloroquine and would, therefore, allow a higher daily dose.
Scientists think HCQ blocks a virus in a few different ways:
- Raising the pH inside endosomes to make them less hospitable to a virus,
- Interfering with the strucutre of ACE-2 surface receptors that bind the virus
- Modulating inflammatory signals called cytokines, which are thought to be a main cause of Covid-19 death.
Since HCQ reduces elevated cytokine activity, the drug is also prescribed for the inflammatory disorders rheumatoid arthritis and lupus.
HCQ is off patent and is produced under many different brand names including: Plaquenil, Hydroquin, Axemal, Dolquine, Quensyl, Quinoric.
HCQ clinical trial data is mixed
Initial results from small-scale clinical studies treating COVID-19 patients with HCQ are contradictory, with some suggesting that HCQ can help theses patients and others suggesting it cannot. Here are a few examples.
A Chinese study from Wuhan showed positive benefit on a 62 person controlled trial. Another French study, led by a colorful character named Didier Raoult, reported significant reductions in viral load in a single arm study. That said, the International Journal of Antimicrobial Agents, which published Didier Raoult’s study, has publicly stated the study did not meet the ‘expected standard’ for trial reporting.
A separate Chinese study with 30 patients failed to see positive results with HCQ. Another French study on 11 patients, published March 30, also reported no benefit from HCQ and zithromax (an antibiotic). Additionally, doctors treating Covid-19 patients at NYU have reported safety issues with 84 of their patients using HCQ (lengthened QT intervals, which is indicative of heart issues.)
Based on the mixed results from these small studies, physicians around the world have begun using HCQ for Covid-19 patients. HCQ is being deployed as either a stand-alone drug or else in conjunction with zinc or the zithromax antibiotic.
In the US, on March 28 the FDA authorized limited, emergency use of the drug for Covid-19 patients. Thousands of Covid-19 patients in NYC have already been treated with HCQ/zithromax.
It’s important to keep in mind that until we see convincing data from large, randomized, placebo-controlled trials, we cannot be certain that HCQ is safe and effective for Covid-19 treatment.
Fortunately, large trials are already underway. One large clinical trial, sponsored by the University of Minnesota, has begun to test the benefits of HCQ. 3,000 patients are enrolling in this trial. The trial is estimated to complete on May 12, 2020.
Join us next week as we continue our discussion of the FDA-approved antivirals being looked at as possible COVID-19 treatments.
This article is adapted from an article originally appearing at: https://www.risingtidebio.com/coronavirus-vaccine-treatment/#antiviral
