"We have reached the end of lockdowns and quarantines as the primary tools in fighting this invisible enemy."
There is hope, indeed. Scientists and medical experts across the globe are working intensely to discover possible treatment protocols against the ravaging COVID-19 virus as the world enters the second year of its destructive spell. Aside from the six (is it seven now?) vaccines produced at warp speed,, the effort is to find lasting treatment or at the very least with the potential to reduce the mortality and transmissibility of this virus. The vaccines, after all, were designed primarily to prevent the spread of the virus and, hopefully, inoculate as many of the population to achieve herd immunity.
This is why the World Health Organization (WHO) and a number of other institutions, including governments, have embarked on programs initially repurposing drugs already used for the treatment of other diseases. Or, as Chinese, Israeli and European scientists are now collaborating on, the eventual discovery of new drugs which can also be repurposed for other diseases.
In the case of the WHO, it has embarked on what it calls a Solidarity PLUS Trial to initially check the potential of three drugs, namely, artesunate, inflixmab and imatinib, chosen by a panel of experts precisely for their potential as COVID-19 treatment. The WHO noted that these drugs were donated by the manufacturers, in this case Ipca, Johnson and Johnson and Novartis, respectively, for the trial with the understanding that these companies will “support access to the drugs at reasonable prices if proven to be effective.” By participating in this trial, the WHO and the manufacturers hope to shorten the period for certification of these drugs for use by the regulatory agencies such as the US FDA and CDC.
Presently, artesunate is being used to treat malaria and other parasitic diseases and has been in the market for over 30 years. As an anti-malaria treatment, it is being evaluated for its anti-inflammatory properties. It is proposed to be intravenously administered for seven days using the standard dose recommended for the treatment of severe malaria. We note that early on two other anti-malaria drugs, chloroquine and hydroxychloroquine, were also touted as possible COVID-19 treatments. In fact, chloroquine was given a US FDA approval for emergency use (EUA) on March 29, 2020 as COVID-19 was surging for clinical trials. This was, however, withdrawn in June 2020.
Like its twin, hydroxychloroquine, it remains possible to use this drug under the direction of a doctor under clinical trials as these two drugs can cause heart rhythm problems. After those initial bursts, we have not heard any kind of progress on these trials. Hopefully, artesunate will not suffer the same fate as the earlier drugs.
On the other hand, imatinib, manufactured by giant pharmaceutical company, Novartis, is considered an inhibitor. Formulated as an oral chemotherapy drug used to treat certain types of cancer, the drug is supposed to reverse pulmonary capillary leak. In a randomized clinical trial performed in the Netherlands, it was noted that it might be able to confer clinical benefits to hospitalized COVID-19 patients without comorbidities or other safety issues. This is also an oral drug and administered once daily for 14 days using the standard maintenance dose except for patients with hematological malignancies, in which case the doses are given over extended periods,
The third drug under the Solidarity PLUS Trial, infliximab, is a TNF alpha inhibitor which has been approved for treatment of certain autoimmune inflammatory conditions for more than 20 years. This Johnson and Johnson drug has demonstrated “favorable efficacy and safety in restricting broad spectrum inflammation, including in elderly populations who are most clinically vulnerable to COVID-19.”
Like the WHO trials, Israeli scientists are busy testing three drugs in a Jerusalem laboratory for possible repurposing as anti-COVID 19 treatments. Global news outlets reported that these three existing drugs in question — darapladib, which currently treats atherosclerosis; the cancer drug flumatinib; and an HIV medicine — all have good prospects as such treatments. Chosen for their ability to target two other proteins not traditionally associated with COVID-19’s spike protein, these drugs are likely to remain effective in spite of mutations. By targeting the envelope protein and the 3A protein variants, Professor Isiah Arkin, the Hebrew biochemist behind the research, noted that “these proteins — especially the envelope protein — hardly change between variants, and even between diseases from the coronavirus family.”
In a report in the Israel Times, Arkin, part of a Hebrew University center that specializes in repurposing existing drugs, said that he screened more than 3,000 medicines for suitability, in what he describes as a needle-in-a-haystack search to “provide a fast track to find treatments as the drugs have already been tried and tested for other diseases.” He noted that even if we had the vaccine, we shouldn’t rest on our laurels and these drugs, once proven effective, can “become part of the arsenal that we use to fight the coronavirus.”
The big difference between the Hebrew University research undertaking and that of the WHO Solidarity trials and other research efforts in other countries is that up until now, the envelope protein has not been seen as a promising target for drugs. But Arkin’s team identified it as an “ion channel, a class of proteins that are located in the membranes of all organisms, which because of their structure respond particularly well to drugs — a quality exploited by pharmaceutical products for high blood pressure, angina and many other conditions,” thus widening the space for experimentation and discovery.
Arkin said: “The prospect of helping to widen the arsenal we have against the coronavirus is what needs to be worked on considering the fact that what allows us to fight HIV, hepatitis and many other diseases, is precisely the fact that we have a variety of treatments — a large arsenal.” Indeed, aside from the vaccines and the mandated health protocols, we have to push hard and accelerate the repurposing and discovery of new treatments to save lives and livelihoods. For if truth be said, we have reached the end of lockdowns and quarantines as the primary tools in fighting this invisible enemy.
