Coronavirus: 'Clamour for HCQ due to anxiety'

Although the antimalarial drug Hydroxychloroquine (HCQ) has been in the news since mid-March as a potential cure for COVID-19, a malaria scientist and an expert on HCQ said that the jury is still out on whether this is the “wonderdrug” a world weary of coronavirus has been waiting for.

Professor Govindarajan Padmanaban (82) was the Director of the Indian Institute of Science (IISc) from 1994 to 1998. Today, he remains a professor emeritus of IISc and is still researching. “I am a molecular biologist by training,” Professor Padmanaban said, adding that his selected area of expertise, malaria, had revealed to him the substantive benefits of HCQ-- and its shortcomings.

Hydroxychloroquine (HCQ), which has been around since World War II and is derived from the bark of the cinchona tree. Like quinine, it is a centuries-old antimalarial drug, which is now generic and easy to get a hold of.

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It has been used extensively to treat malaria and other medical conditions such as lupus, but its efficacy is rapidly wearing off in the treatment of malaria itself, with the drug having no efficacy against one of the two plasmodiums causing malaria-- plasmodium falciparum and plasmodium vivax.

Where the drug entered the coronavirus picture is less clear, although Professor Padmanaban described HCQ’s manifestation in the popular imagination as a “wonder drug” as being largely a product of the times.

“These are desperate times, people are looking for all kinds of molecules and antibiotics to find a quick fix,” Professor Padmanaban said.

He added that he believed two early, published research papers were largely responsible for the drug being, what he described as “hyped up” by US President Donald Trump. One of the papers was by a Chinese research group in March, in which the scientists claimed to have used chloroquine phosphate in almost 10 hospitals in Wuhan, with “very good” results.

There is another paper by a French Group, which saw HCQ tested among 24 patients, which were not selected at random as per standard testing norms. Professor Padmanaban said that he believes that efficiency of the drug in the malaria-causing plasmodium, coupled with its readily available status has prompted the scientists to extrapolate its efficacy against the SARS-Cov-2 virus.

“How the drug works is that it gets into the lysosomes inside the malarial parasite. These are spaces inside the cell, protected by a membrane, which act like an internal stomach. They contain the enzymes and cofactors required for the parasite to safely break down haemoglobin and lock away the toxic haem waste products, which the parasite normally converts into an inert molecule known as hemozoin,” Professor Padmanaban said.

As in the human stomach, the pH is lower inside the lysosome than in the rest of the cell, and this acidic environment causes HCQ to build-up to the point where it cannot diffuse back out. Once inside, it causes a build-up of haem that ultimately kills the parasite.

“So, this is one of the mechanistic operations of HCQ on the malaria-causing plasmodium. However, at present there is no proof that this mechanism is being repeated against the Sars-CoV-2 virus,” Professor Padmanaban added.

Although in-vitro tests a decade ago showed that the drug had some efficacy against the 2003 SARS virus, Dr Padmanaban pointed out these tests were all culture studies.

“There is a lot of difference between what happens invitro and what happens inside an animal or in the human because of factors like absorption, metabolism, blood level...etc,” he said.

He clarified, however, that although with many countries now starting human clinical trials, that the questions about how effective the drug would be against the coronavirus would soon be answered.

“What is needed are a large number of clinical trials to determine the efficacy of HCQ against the Sars-CoV-2 virus. There are many international labs which have started these trials and a massive amount of data will be generated. Within a month or so, we will get enough information about whether it works or not. Soon, we will know if the hopes which have been placed on this drug are justified,” he said.