The Phnom Penh Post

Which drugs are effective for Covid-19?

- Leonny Hartiadi and Audrey Crystalia

THE Coivd-19 pandemic has spread to 210 countries. As of Wednesday, more than 3.2 million people had tested positive for the virus and 256,422 people had died.

Many reports are circulatin­g about possible drugs, causing confusion among the public.

Several types of drugs are being studied to treat Covid-19. Most of the drugs are antiviral drugs that have previously been used for other conditions. Among the antiviral medication­s are favipiravi­r, or Avigan, which was used to treat influenza in Japan; remdesivir, which was tested on Ebola; ritonavir-lopinavir, an antiviral drug given to HIV patients; and ribavirin which is used for hepatitis C and other viral hemorrhagi­c fevers.

The Food and Drug Monitoring Agency (BPOM) has released its recommenda­tions for Covid-19 therapy in Indonesia. In Indonesia, the antiviral therapy to be given to patients with moderate and severe symptoms is favipiravi­r.

Other countries and the World Health Organisati­on have not yet released specific guidelines on Covid19 drug treatments, but we can see that various antiviral medication­s are being used in other countries. The most common are favipiravi­r, remdesivir, lopinavir-ritonavir and ribavirin.

Favipiravi­r and remdesivir work against viruses by inhibiting the RNAdepende­nt RNA polymerase (RdRP), an enzyme needed by viruses to replicate their genetic material in human cells. Ribavirin also works by inhibiting RdRP as well as interferin­g with the replicatio­n of viral genetic material in other ways. In addition, ribavirin was also shown to increase the immunity of human cells to viruses.

Lopinavir-ritonavir was found to hinder the activity of a type of protease needed by viruses to replicate.

The replicatio­n of viruses is directly related to the severity of the disease. Data suggests that a higher SarsCoV-2 viral load – a measure of the amount of the virus in a patient’s body – is related to more severe symptoms. Therefore, the more we can inhibit viral replicatio­n and cause a lower viral load, the more we can hopefully alleviate the severity of the disease.

Fav ipirav ir, remdesiv ir, lopinav irritonav ir and ribav irin have demonstrat­ed ef fectivenes­s against SarsCoV-2 in v itro – meaning in laborator y tests using cell cultures. To date, t here is no strong ev idence of any drugs being effective against t he v irus in humans, regardless of t he few case studies claiming treatments were effective on patients.

Several ongoing clinical trials of the antiviral medication­s are expected to conclude at the end of the year. Only then can we obtain more evidence about which drugs, if any, effectivel­y treat Covid-19.

Drugs used to treat other diseases are also being studied to treat Covid19. These are chloroquin­e (CQ) and hydroxychl­oroquine (HCQ). These repurposed drugs have been used to treat malaria and chronic inflammato­ry diseases. HCQ is a derivate of CQ with fewer toxic effects than CQ.

In vitro studies suggest that both CQ and HCQ are efficient at inhibiting Sars- CoV-2. Both drugs prevent the virus’ entry and modulate the immune system. Clinical trial data from both drugs is still limited and inconclusi­ve given small sample sizes with poorly controlled or uncontroll­ed clinical trials. Numerous randomised control trials are ongoing to establish the effectiven­ess of these drugs on Covid-19. Despite lacking convincing evidence to support the use of CQ, China’s medical advisory board has suggested its inclusion in treatment guidelines, making CQ the first drug used in China and overseas to treat moderate to severe cases of Covid-19.

Type-1 interferon­s (IFNs) are another potential candidate. IFNs are normally produced by our body in response to viral infections. Therefore, IFNs have general antiviral properties. Previously, IFNs were investigat­ed for the treatment of the Middle East Respirator­y Syndrome (Mers).

The Mers virus belongs to the same genus as Sars-CoV-2: betacorona­virus. The close relationsh­ip between these viruses is the basis for the use of IFNs to treat Covid-19. Although current Chinese guidelines list interferon­s as an alternativ­e for combinatio­n therapy, the research results are conflictin­g and no clinical trials have been completed so far.

Monoclonal antibodies against interleuki­n-6, a protein produced by various cells to trigger inflammati­on, have also been used as adjunctive therapy in China and Singapore.

Known as tocilizuma­b, these antibodies are administer­ed to alleviate the “cytokine storm” that causes profound damage to the lungs and other organs in Covid-19 patients. In several case reports, this treatment was found to be successful on Covid-19 patients experienci­ng severe forms of the illness. One small study with no control reported clinical improvemen­t in 91 per cent of patients. Further clinical studies are ongoing to confirm this finding.

Due to t he lack of cl i nica l t r ia ls on t hese dr ugs, t hey ca n only be g iven to Cov id-19 pat ients under close medica l super v ision.

Another treatment uses convalesce­nt plasma: plasma extracted from the blood of recovered Covid-19 patients. This plasma contains antibodies that neutralise Sars-CoV-2.

An early study showed that a single dose of 200ml of convalesce­nt plasma given to Covid-19 patients with severe forms of the illness showed promising results. Therefore, a large clinical trial in the US is underway. The Food and Drug Administra­tion is encouragin­g recovered patients to donate their blood to support the study. US actor Tom Hanks has reportedly offered to donate his blood plasma following his recovery from Covid-19.

The above informatio­n is important for people to know and understand so they can sort out the informatio­n available. Not all of what is circulated is true, and websites may exaggerate informatio­n with a catchy title. For a drug to be approved for use on humans, the drug needs to undergo rigorous testing through invitro studies, pre-clinical trials using animals and clinical studies to demonstrat­e its safety and efficacy.

 ?? AFP ?? An engineer works at the Quality Control Laboratory on an experiment­al vaccine for the Covid-19 coronaviru­s at the Sinovac Biotech facilities in Beijing, China, on April 29.
AFP An engineer works at the Quality Control Laboratory on an experiment­al vaccine for the Covid-19 coronaviru­s at the Sinovac Biotech facilities in Beijing, China, on April 29.

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