Thousands of Scientists Are Working to Find a Cure for COVID-19: Which Studies Stand Out?

When?

Recently, everyone has had one question in mind: "COVID-19, the disease caused by the novel coronavirus: when will a cure be found?" Thousands of scientists worldwide are conducting research to answer this question. Although we get a little closer to the hoped-for outcome every day, obstacles remain. This article discusses new research approaches and the progress made so far.

Viruses introduce their genetic material into human cells. When these cells read their genetic instructions to make proteins, they also produce viral proteins. These proteins are then used to form new viruses, which invade other human cells. Coronavirus attacks cells in the respiratory tract, causing the flu-like symptoms seen in infected people. In later stages, however, it can cause symptoms more severe than influenza.

Mapping the Novel Coronavirus at Incredible Speed

Many scientists are trying new vaccines and drugs to find a solution. However, the Coronavirus Research Group at the University of California, San Francisco’s Quantitative Biosciences Institute took a different approach. Institute director Dr. Nevam Krogan and his team began mapping the proteins viruses use to attach to our cells and transfer their genetic material in 2011, working on HIV and identifying 453 proteins. They also applied similar mapping methods to Ebola and dengue viruses. Now they have done so for the novel coronavirus (SARS-CoV-2). A project that would normally take around 2 years, thanks to collaboration between 22 laboratories, was completed within a few weeks and published on 22 March. Researchers produced a map of the 332 proteins responsible for interactions between human cells and coronavirus. The aim is to target the different protein combinations pathogens use to attach to host cells, preventing the virus from entering and multiplying inside our cells. Rather than testing entirely new drugs, they listed medicines that included some already approved by the US Food and Drug Administration (FDA) and previously used for other diseases: 62 drugs in total. Working with other universities and institutes, they began testing the selected drugs under laboratory conditions. Dr. Garcia-Sastre, the head of a private medical school in New York collaborating with the team, said testing in monkey cells had begun, adding: "Even if we obtain an effective result in the laboratory, we cannot say for certain that it will be applicable to COVID-19. We first need to establish an appropriate dose for the human body and identify its adverse effects."

The Video Above: a simulation of the SARS-CoV2/ACE2 interaction from DE Shaw Research. A focus of COVID-19 treatment research is finding a molecule that blocks the chemical interaction between the Spike protein, shown in green, and the ACE2 receptor, shown in red.

Testing Approved Drugs Because Discovering New Molecules Takes Time

Alongside this approach, many other studies continue. One involves remdesivir, an antiviral that generally works by preventing viruses from producing new genetic material. In February studies, remdesivir eliminated coronavirus in infected cells "in the laboratory." To establish its safety and efficacy in COVID-19 patients, 5 clinical trials were launched.

In completed clinical trials for COVID-19, most drugs used as treatment have been off-label: their actual approved indication is not COVID-19, but another infectious disease. The only exception is plasma transfusion therapy, which is used under authorization only for testing in critically ill patients and has not yet received FDA approval. Other off-label drugs being tried for COVID-19 include danoprevir, approved for hepatitis C infection, and hydroxychloroquine (Plaquenil), approved for malaria.

CRISPR Genome-Editing Technology

Another promising report came in an article published on 14 March: a genetic approach to COVID-19. Tim Abbott, a doctoral student in Stanford University’s Department of Bioengineering, showed that CRISPR technology could potentially be used against coronavirus. CRISPR-Cas9 is a distinctive technology that allows genetic material to be added, removed or changed at different sites in the genome.

The team reported laboratory results in which the method eliminated 90% of coronavirus in solution, suggesting it might also be sufficient to stop the disease in humans. However, they stressed that this was a proof-of-concept stage, rather than a method ready for immediate hospital use. Although they said human testing would require at least 4 or 6 months, a method with demonstrated laboratory activity is exciting for the future.

An Antiparasitic Drug Shows Activity in the Laboratory

A study published on 3 April discussed ivermectin, an antiparasitic drug approved by the FDA for head lice. An Australian team reported that ivermectin eliminated coronavirus within 48 hours "in the laboratory," with a substantial reduction in virus numbers within the first 24 hours. Calling it an important potential treatment, the team said the next step was to determine an appropriate dose for COVID-19 patients and investigate clinical efficacy.

The Vaccine Closest to Approval

The first human COVID-19 vaccine trial began in early March with biotechnology company Moderna’s mRNA-1273 vaccine.

The mRNA-1273 trial, involving 45 healthy men and nonpregnant women aged 18-55, is still in phase-I, with results expected in June 2021. Nevertheless, its use in healthcare workers in the USA before the trial results are available is being discussed.

On 30 March, Johnson & Johnson announced the selection of a vaccine candidate and said that, together with the Biomedical Advanced Research and Development Authority (BARDA), it expected to begin human clinical studies by September 2020 and was possibly preparing the first batches of a COVID-19 vaccine.

The Antimalarial Plaquenil Has Not Yet Delivered the Hoped-For Results

Despite interim results suggesting reduced COVID-19 viral load in an ongoing trial of hydroxychloroquine (Plaquenil) with azithromycin at Aix Marseille University in France, antiviral combinations have not achieved the desired results. Results from other trials investigating hydroxychloroquine alone have not been announced.

Although many clinical trials are underway for COVID-19, only 5 have successfully met their primary endpoint. First, a drug normally approved in Japan to treat influenza (flu) is favipiravir, which showed promising results in 2 clinical trials as first-line treatment. One favipiravir study showed activity against COVID-19, with fewer adverse effects and better treatment outcomes than lopinavir/ritonavir used as second-line treatment. Initially approved for HIV/AIDS, lopinavir/ritonavir was tested as the primary intervention in two clinical trials: one failed to meet its primary endpoint and the other was inconclusive. This combination did not significantly accelerate clinical improvement, reduce mortality or lower throat viral RNA levels in COVID-19 patients.

Thus, although some trials are encouraging, the results reported so far have not identified the effective COVID-19 drugs we eagerly await. Most current clinical trials are single-country studies with limited populations of 10 to 240 participants. In April, we will learn more about trial results for danoprevir, meplazumab and favipiravir.

We will continue following these studies closely and keeping you informed. While many studies are being conducted worldwide, our responsibility is to stay at home. Please stay home and stay healthy, for yourself and your loved ones.

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