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Drugs that may Treat COVID-19 |
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Drugs that may Treat COVID-19 ( some probably not)
The nucleotide-analogue drug that has gained the most attention for fighting SARS-CoV-2 is remdesivir. It was originally developed by Gilead Sciences, an American biotechnology firm, for use against Ebola fever. That work got as far as indicating that the drug was safe in humans, but because antibody therapy proved a better way of treating Ebola, remdesivir was put to one side. Laboratory tests, though, showed that it worked against a range of other rna-based viruses, including sars-cov, and the same tests now show that it can block the replication of SARS-CoV-2, too. There are now various trials of remdesivir’s efficacy in covid-19 patients. Gilead is organising two in Asia that will, together, involve 1,000 infected people. They are expected to yield results in mid- to late-April. Other nucleotide analogues are also under investigation. When they screened seven drugs approved for other purposes for evidence of activity against SARS-CoV-2, a group of researchers at the State Key Laboratory of Virology in Wuhan saw some potential in ribavirin, an antiviral drug used in the treatment of, among other things, hepatitis c, that is already on the list of essential medicines promulgated by the World Health Organisation (who). Nucleotide analogues are not the only antiviral drugs. The second generation of anti-hiv drugs were the “protease inhibitors” which, used along with the original nucleotide analogues, revolutionised the treatment of the disease. They targeted an enzyme with which hiv cuts big proteins into smaller ones, rather as one of SARS-CoV-2’s nsps cuts its big polyproteins into more little nsps. Though the two viral enzymes do a similar job, they are not remotely related—hiv and SARS-CoV-2 have about as much in common as a human and a satsuma. Nevertheless, when Kaletra, a mixture of two protease inhibitors, ritonavir and lopinavir, was tried in sars patients in 2003 it seemed to offer some benefit. Another drug which was developed to deal with other rna-based viruses—in particular, influenza—is Favipiravir (favilavir). It appears to interfere with one of the nsps involved in making new rna. TRUMP HYPED:- But existing drugs that might have an effect on SARS-CoV-2 are not limited to those originally designed as antivirals. Chloroquine, a drug mostly used against malaria, was shown in the 2000s to have some effect on sars-cov; in cell-culture studies it both reduces the virus’s ability to get into cells and its ability to reproduce once inside them, possibly by altering the acidity of the Golgi apparatus. Camostat mesylate, which is used in cancer treatment, blocks the action of proteases similar to tmprss2, the protein in the cell membrane that activates the spike protein. Not all drugs need to target the virus. Some could work by helping the immune system. Interferons promote a widespread antiviral reaction in infected cells which includes shutting down protein production and switching on rna-destroying enzymes, both of which stop viral replication. Studies on the original sars virus suggested that interferons might be a useful tool for stopping its progress, probably best used in conjunction with other drugs Conversely, parts of the immune system are too active in covid-19. The virus kills not by destroying cells until none are left, but by overstimulating the immune system’s inflammatory response. Part of that response is mediated by a molecule called interleukin-6—one of a number of immune-system modulators that biotechnology has targeted because of their roles in autoimmune disease. Actemra (tocilizumab) is an antibody that targets the interleukin-6 receptors on cell surfaces, gumming them up so that the interleukin-6 can no longer get to them. It was developed for use in rheumatoid arthritis. China has just approved it for use against covid-19. There are anecdotal reports of it being associated with clinical improvements in Italy. While many trials are under way in China, the decline in the case rate there means that setting up new trials is now difficult. In Italy, where the epidemic is raging, organising trials is a luxury the health system cannot afford. So scientists are dashing to set up protocols for further clinical trials in countries expecting a rush of new cases. Dr Farrar said on March 9th that Britain must have its trials programme agreed within the week. There are already concerns that, should one of the promising drugs prove to be useful, supplies will not be adequate. To address these, the who has had discussions with manufacturers about whether they would be able to produce drugs in large enough quantities. Generic drug makers have assured the organisation that they can scale up to millions of doses of ritonavir and lopinavir while still supplying the hiv-positive patients who rely on the drugs. Gilead, meanwhile, has enough remdesivir to support clinical trials and, thus far, compassionate use. The firm says it is working to make more available “as rapidly as possible”, even in the absence of evidence that it works safely. |
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