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remdesivir

Molnupiravir effective against Omicron, can reduce deaths: Study

by Medically Speaking Team February 16, 2022

According to a new study, a five-day course of the antiviral medicine Molnupiravir may be effective against the highly contagious Omicron and other strains of concern (VOCs).

Molnupiravir may be superior to monoclonal antibodies and Remedivisir, according to the study.

“From the available evidence, Molnupiravir appears to be a reasonably useful drug in reducing deaths and hospitalisation in adult patients with COVID-19 having high risk, with a relatively lower cost. Molnupiravir could be a useful drug in non-pregnant unvaccinated adults with COVID-19 who are at increased risk of severity including hospitalization,” said Dr. Anoop Misra, Padma Shri, Executive Chairman and Director, Diabetes and Endocrinology, Fortis C- DOC.

The study, published in the journal, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, was conducted by a team of doctors at Fortis C-DOC, GD Hospital and Diabetes Institute, Jawaharlal Nehru Medical College and Hospital, and the Diabetes Foundation.

It pointed out that “subgroup analysis found Molnupiravir was effective irrespective of strain although no data is available for its effect on Omicron in particular”, stated the study.

“Unlike monoclonal antibodies, the mechanism of action of Molnupiravir is independent of mutations in the spike protein, and it is expected to work against Omicron, theoretically. Indeed, in vitro study of VeroE6-GFP cells does indicate that Molnupiravir retain their activity against VOCs of Alpha, Beta, Gamma, Delta, and Omicron,” the journal added.

“However, Molnupiravir is effective only when used within five days from the onset of Omicron symptoms. Inappropriate use without assessing risk may pose an unknown long-term risk of public concern,” cautioned Dr. Misra.

February 16, 2022 0 comment

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Current anti-COVID pills work well against omicron, but antibody drugs are less effective, study finds

by Medically Speaking Team January 27, 2022

written by Medically Speaking Team

The drugs behind the new pills to treat COVID-19 remain very effective against the omicron variant of the virus in lab tests, according to a new study.

However, lab tests also showed that the available antibody therapies — typically given intravenously in hospitals — are substantially less effective against omicron than against earlier variants of the virus. Some antibodies have entirely lost their ability to neutralize omicron at realistic dosages.

If the ability of the antiviral pills to combat omicron is confirmed in human patients, it would be welcome news. Public health officials expect the pills to become an increasingly common treatment for COVID-19 that will reduce the severity of the disease in at-risk patients and decrease the burden of the pandemic.

For now, the pills remain in short supply during the current omicron wave, which has broken case records in the U.S. and other countries.

The findings corroborate other studies that show most available antibody treatments are less effective against omicron. Drug makers could design, test and produce new antibody drugs targeted at the omicron variant to overcome the limitations of current therapies, but this process would take months.

“The bottom line is we have countermeasures to treat omicron. That’s good news,” says Yoshihiro Kawaoka, the University of Wisconsin-Madison lead of the study and virologist at the UW School of Veterinary Medicine and the University of Tokyo. “However, this is all in laboratory studies. Whether this translates into humans, we don’t know yet.”

Kawaoka and his collaborators at UW-Madison and the National Institute of Infectious Diseases in Tokyo published their findings in the New England Journal of Medicine on Jan. 26.

The clinically available pills and antibodies were designed and tested before researchers identified the omicron variant, which differs significantly from earlier versions of the virus. When omicron was identified, scientists feared that these differences, caused by mutations in the viral genome, might reduce the effectiveness of drugs designed to treat the original version of the virus.

In lab experiments using non-human primate cells, Kawaoka’s team tested a suite of antibody and antiviral therapies against the original strain of the COVID-19 virus and its prominent variants, including the alpha, delta and omicron strains.

Merck’s pill molnupiravir and the intravenous drug remdesivir were just as effective against the omicron variant as they were against earlier viral strains.

Instead of testing Pfizer’s Paxlovid pill, which is designed to be taken orally, the team tested a related drug by Pfizer that is given intravenously. The two drugs disrupt the same part of the viral machinery. The researchers found that the intravenous form of the drug retained its effectiveness against omicron, and this version is currently in clinical trials.

All four antibody treatments the researchers tested were less effective against omicron than against earlier strains of the virus. Two treatments, sotrovimab by GlaxoSmithKline and Evusheld by AstraZeneca, retained some ability to neutralize the virus. However, they required anywhere from 3 to 100 times more of the drugs to neutralize omicron compared to earlier versions. AstraZeneca’s antibodies are not approved for use in the U.S.

Two antibody treatments by Lilly and Regeneron were unable to neutralize omicron at common dosages.

These findings are expected given how the omicron variant differs from earlier strains of SARS-CoV-2, the COVID-19 virus. Omicron has dozens of mutations in the spike protein, which the virus uses to enter and infect cells. Most antibodies were designed to bind to and neutralize the original spike protein and major changes to the protein can make antibodies less likely to attach to it.

In contrast, the antiviral pills target the molecular machinery the virus uses to make copies of itself inside cells. The omicron variant only has a few changes to this machinery, which makes it more likely that drugs will retain their ability to disrupt this replication process.

The Kawaoka lab is now studying new antibody candidates to identify ones that could neutralize the omicron variant.

Source: University of Wisconsin-Madison

January 27, 2022 0 comment

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India reduces use of Remdesivir, Tocilizumab, multivitamins, steroids as part of new Covid guidelines

by Medically Speaking Team January 18, 2022

written by Medically Speaking Team

For the treatment of COVID-19, India has reduced the usage of the investigational medicine Remdesivir and the immunosuppressive drug Tocilizumab.

The revised treatment guidelines for COVID-19 management were issued on Monday by the Indian Council of Medical Research (ICMR), the country’s highest medical research agency.

Remdesivir should only be evaluated in individuals who have had their symptoms for at least 10 days and require supplementary oxygen, according to the updated guidelines.

It has been underlined, however, that the medicine cannot be given to patients who are on a ventilator or who are receiving extracorporeal membrane oxygenation (ECMO), a treatment that employs a pump to transfer blood through an artificial lung back into a very ill baby’s bloodstream.

While it states that doctors can “consider Remdesivir for five days to treat hospitalised patients with COVID-19”, it also mentions that “no evidence of benefit for treatment more than five days”.

Designed by AIIMS and ICMR-led COVID-19 National Task Force, the latest protocol, apart from curtailing the role of controversial drug Remdesivir, has waived off the use of multivitamin pills which was earlier advised for the treatment of mild cases.

Under the management of mild Covid disease, the list of “must-do” activities includes hydration, anti-pyretics and anti-tussive, removing the need to pop multivitamins.

This means that when a patient is suffering mild symptoms with no shortness of breath or low oxygen in blood (SpO2), they must keep themselves hydrated, consume anti-fever medicines and medicines to suppress cough.

For moderate cases, the protocol clarifies “there is no evidence for benefit for injectable steroids” in patients who are not requiring oxygen supplementation, or on continuation after discharge. The move is triggered by the increase in cases of black fungus after the second wave due to the overuse of steroids.

A total of 51,775 cases of mucormycosis or ‘Black Fungus’ had been reported till November 29, Union Health Minister Mansukh Mandaviya informed the Lok Sabha in December.

Discouraging the overuse of steroids, the protocol for both moderate and severe patients notes that “anti-inflammatory or immunomodulatory therapy (such as steroids) can have risk of secondary infection such as invasive mucormycosis when used too early, at higher dose or for longer than required.”

Additions in the new guidelines

The latest guidelines include “blood sugar” as an additional test under the laboratory monitoring protocol for both severe and moderate patients.

Earlier, the protocol suggested monitoring of “CRP and D-dimer, complete blood count (CBC), kidney function test (KFT), liver function test (LFT) and IL-6 levels”.

It also suggests that if cough, in mild cases, persists for more than two to three weeks, investigate for tuberculosis and other conditions. The protocol also added people with “active tuberculosis” under the category of high risk for severe disease or mortality.

For the mild, the new treatment does not promote the prescription of multivitamins.

Change inTocilizumab guidelines

It also mentions that Tocilizumab can be considered for patients who meet five criteria, including that the patient should not have active tuberculosis, fungal or any systemic bacterial infection.

The immunosuppressant drug can only be given to patients who are on oxygen therapy or on ventilators but not responding to steroids. Also, the inflammatory markers should be significantly raised. But the drug should preferably be given along steroids, it mentions.

The guidelines also emphasise that in case of administration of the drug, long-term follow-up should be done for secondary infections such as reactivation of TB or flaring of herpes.

Earlier, the guidelines included a wider set of patients who could be given the drug as it can be given to people with “presence of severe disease” without mentioning any criteria for patient selection.

Carefully selected subsets of patients

According to experts treating Covid-19 patients in hospitals across India, the latest guidelines are “evidence-based”, especially on reducing the role of Tocilizumab. However, they pointed out that Remdesivir should be on its way out as several trials have already proved that the drug is of no use in Covid-19.

“Remdesivir has been continued but with lots of caveats,” said Sumit Ray, head of the department of Critical Care Medicine at Holy Family Hospital. “The ministry is playing safe. The WHO guidelines have weak recommendations against its use. The time for Remdesivir is running out. It remains a drug in search of a disease. The role of antivirals in a rapidly replicating respiratory virus is going to be very questionable.”

Solidarity trial has not approved Remdesivir, experts said. The trial concluded that Remdesivir, Hydroxychloroquine, Lopinavir, and interferon regimens had little or no effect on hospitalised patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.

“Death occurred in 301 of 2,743 patients receiving Remdesivir and in 303 of 2,708 receiving its control, hence no difference was observed,” said Dr SP Kalantri, Professor of Medicine, Mahatma Gandhi Institute of Medical Sciences, Maharashtra while suggesting that “we also need to ask what additional advantage does Remdesivir offer in hospitalised hypoxic patients who are already on dexamethasone — a steroid that has been shown to save lives in critically ill Covid patients.”

According to Dr Yatin Mehta, chairman of Institute of Critical Care and Anaesthesiology, Medanta, the move to retain Remdesivir makes sense.

“A new study on Remdesivir has shown significant benefit when given to patients at home for three days. However, these guidelines might have been formed prior to the release of the latest study,” he said, hinting that if useful, Remdesivir may also be considered for use in home settings.

India’s clamour for Remdesivir has been a misfit against the World Health Organization (WHO)’s advice. Earlier, WHO had said that there is no evidence to suggest that the antiviral drug can effectively treat Covid-19 patients.

However, guidelines of Tocilizumab are fine, Mehta said.

Ray from Holy Family Hospital emphasised that “the role for Tocilizumab lies in an extremely small carefully chosen subset”.

The problem with India is the clinicians’ ability to make those judgements. Sometimes, he said, these judgements are not well informed due to a lack of continuing medical education to upgrade one’s knowledge of disease processes.

“The side effects of immunosuppression with either high dose steroids or Tocilizumab are very serious, thus, patient selection has to be carefully evaluated, so that the benefits have a fair chance of outweighing the risks.”

This post has been published from a syndicate feed with some changes to the text and headline.

January 18, 2022 0 comment

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Mutation associated to remdesivir resistance discovered in Covid patient.

by Medically Speaking November 11, 2021

written by Medically Speaking

Researchers discovered resistance to Gilead Sciences Inc.’s antiviral remdesivir in coronavirus samples taken from an immunocompromised patient being treated with the medicine for a chronic Covid-19 infection.

Similar resistance-causing mutations have been created in lab trials, but have not previously been documented in patients treated with the injectable drug, according to Shiv Gandhi, Akiko Iwasaki, and colleagues at Yale University School of Medicine. The patient, a woman in her 70s who had been treated for non-Hodgkin’s lymphoma, caught Covid in May 2020. Remdesivir helped alleviate symptoms, but wasn’t able to completely clear the infection. It persisted for several months, affecting her sense of smell.

Genetic analysis of the virus showed that it acquired a mutation during treatment that appeared to reduce the effectiveness of the drug, the first cleared for Covid-19. The infection was successfully treated with monoclonal antibody therapy, which also led to a recovery of her sense of smell.

“While the finding is limited to a single case and requires confirmation of its generalizability in larger patient populations, it suggests that remdesivir can impart selective pressure” in patients to drive evolution of the virus, the researchers said in a study, which was released on medRxiv ahead of peer-review and publication.

The scientists found the mutation, called E802D, reduced the fitness of the SARS-CoV-2 virus that causes Covid-19. They said the case illustrates the importance of monitoring for remdesivir resistance and the potential benefit of using a combination of therapies in immunocompromised patients.

November 11, 2021 0 comment

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Scientists propose repurposing anti-malarial drug Mefloquine to fight COVID-19

by Medically Speaking Team July 2, 2021

written by Medically Speaking Team

Japanese scientists are scanning the possibility of using an anti-malarial drug called mefloquine. In a breakthrough study, a team of scientists from Tokyo University of Science (along with scientists from the National Institute of Infectious Diseases, Kyushu University, The University of Tokyo, Kyoto University, Japanese Foundation for Cancer Research, and Science Groove Inc.) have identified an anti-malarial drug, mefloquine (which is incidentally a derivative of hydrochloroquine), that is effective against SARS-CoV-2.

Lead scientist Dr. Watashi says, “To identify drugs with higher antiviral potency than existing antivirals, we first screened approved anti-parasitic/anti-protozoal drugs. We found that mefloquine had the highest anti-SARS-CoV-2 activity among other tested compounds like quinoline derivatives (hydrochloroquine) laboratory human lung cells.”

Explaining the mefloquine’s mechanism of action, Dr. Watashi said, “In our cell assays, mefloquine readily reduced the viral RNA levels when applied at the viral entry phase but showed no activity during virus-cell attachment. This shows that mefloquine is effective on SARS-COV-2 entry into cells after attachment on cell surface.”

Thus, to bolster mefloquine’s anti-viral activity, the scientists looked into the possibility of combining it with a drug that inhibits the replication step of SARS-CoV-2: Nelfinavir. Interestingly, they observed that the two drugs acted in “synergy” and the drug combination showed greater anti-viral activity than either showed alone, without being toxic to the cells in the cell lines themselves.

Mathematical modelling of the effectiveness of mefloquine depicted predict that mefloquine could reduce the overall viral load in affected patients to under 7% and shorten the ‘time-till-virus-elimination’ by 6.1 days, and thus is potential in treating real-world cases. Study is yet to succeed the clinical trials, but the world can hope that mefloquine becomes a drug used to effectively treat patients with COVID-19.

Some approved drugs for COVID-19, like hydroxychloroquine, lopinavir, and interferon, have already been put to clinical use against SARS-CoV-2 without well establishing their clinical efficacies, due to the severity of the pandemic. Subsequent randomized trials have not been able to yield a consensus on the efficacy of these drugs. Only remdesivir has been approved for clinical use against severe COVID-19, although its efficacy is still being debated.

Published: Frontiers in Microbiology.

July 2, 2021 0 comment

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Remdesivir not effective for treatment of Covid, Docs raise questions upon Pharma companies

by Medically Speaking Team May 25, 2021

written by Medically Speaking Team

Amidst rampant black marketing of Remdesivir, doctors say it is a false perception that this injection is important for treatment of Covid patients and that it is a game-changer.

In corona 1.0, it was Hydroxychloroquine (HCQ). Its sale skyrocketed once Donald Trump called it a wonder drug. In 2.0 version of corona it is Remdesivir. And the efficacy of both the drugs in treating COVID-19 is quite doubtful. Are pharma companies then playing with people’s sentiments and minting money in this pandemic.

The question is raised because amidst the black marketing of Remdesivir, doctors say it is a false perception that this injection is important for treatment of Covid patients and that it is a game-changer.

Nodal officer for Covid at KGMU Dr Surya Kant Tripathi said he is against the use of Remdesivir and that it is a false perception that it is a game-changer.

“Studies are totally against it and it was propagated for the treatment of severe pneumonia, but the trial stopped later. In very selective cases, doctors are using it but I am not using it in the treatment of Covid patients,” he said.

President of People’s Health Organisation Dr Ishwar Gilada also said that it is a totally false perception that Remdesivir is important for COVID-19 treatment.

Giving a backgrounder, he said that the drug was first used in 2010 for Hepatitis C, but was not found to be effective, and was later used for other diseases.

“When coronavirus outbreak happened, many drugs were repurposed. A random trial with Remdesivir showed that it did not prevent death but only lessened hospitalisation by two days,” he said.

He said no guidelines have been issued regarding the usage of Remdesivir, but a lot of doctors are in a habit of using it and patients themselves start demanding it.

“The doctors started using it and vouching that it was effective but it does not help and there is no scientific evidence,” he said.

He added that hospitals are also making money because they are getting it for Rs 800-1,000 but they are selling it at higher costs.

“Patients insist on using it because they are not very satisfied on being given only a couple of medicines for Covid treatment. What remains crucial for treatment is the oxygen supply and steroids,” he said.

May 25, 2021 0 comment

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SARS-CoV-2 research: Second possible effective mechanism of Remdesivir discovered

by Medically Speaking Team May 12, 2021

written by Medically Speaking Team

When a cell is infected, SARS-CoV-2 not only causes the host cell to produce new virus particles. The virus also suppresses host cell defence mechanisms. The virus protein nsP3 plays a central role in this. Using structural analyses, researchers at Goethe University in cooperation with the Swiss Paul Scherrer Institute have now discovered that a decomposition product of the virostatic agent remdesivir binds to nsP3. This points to a further, previously unknown effective mechanism of remdesivir which may be important for the development of new drugs to combat SARS-CoV-2 and other RNA viruses.

The virostatic agent remdesivir was developed to disrupt an important step in the propagation of RNA viruses, to which SARS-CoV-2 also belongs: the reproduction of the virus’s own genetic material. This is present as RNA matrices with which the host cell directly produces virus proteins. To accelerate the production of its own proteins, however, RNA viruses cause the RNA matrices to be copied. To do so, they use a specific protein of their own (an RNA polymerase), which is blocked by remdesivir. Strictly speaking, remdesivir does not do this itself, but rather a substance that is synthesized from remdesivir in five steps when remdesivir penetrates a cell.

In the second of these five steps, an intermediate is formed from remdesivir, a substance with the somewhat unwieldy name GS-441524 (in scientific terms: a remdesivir metabolite). GS-441524 is a virostatic agent as well. As the scientists in the group headed by Professor Stefan Knapp from the Institute for Pharmaceutical Chemistry at Goethe University Frankfurt have discovered, GS-441524 targets a SARS-CoV-2 protein called nsP3. nsP3 is a multifunctional protein, whose tasks include suppressing the host cell’s defence response. The host cell is not helpless in the face of a virus attack, but activates inflammatory mechanisms, among other things, to summon the aid of the cell’s endogenous immune system. nsP3 helps the viruses suppress the cell’s calls for help.

Professor Stefan Knapp explains: “GS-441525 inhibits the activities of an nsP3 domain which is important for the reproduction of viruses, and which communicates with human cellular defence systems. Our structural analysis shows how this inhibition functions, allowing us to lay an important foundation for the development of new and more potent antiviral drugs — effective not only against SARS-CoV-2. The target structure of GS-441524 is very similar in other coronaviruses, for example SARS-CoV and MERS-CoV, as well in a series of alphaviruses, such as the chikungunya virus. For this reason, the development of such medicines could also help prepare for future virus pandemics.”

May 12, 2021 0 comment

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2 lab technicians, one nurse arrested for black marketing of Remdesivir

by Medically Speaking Team May 12, 2021

written by Medically Speaking Team

A nurse, two lab technicians and a pharmacy store owner arrested for black marketing of Remdesivir injections in Shahdol. ASP Mukesh Vaish said, “Six injections, mobile phones and over Rs 6 lakhs cash recovered from their possession. A case is registered and strict action will be taken.”

May 12, 2021 0 comment

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‘Remdesivir will be available at govt prices’

by Medically Speaking Team May 7, 2021

written by Medically Speaking Team

Union Minister Nitin Gadkari said on Thursday that the Centre will boost the production of anti-viral drug Remdesivir and the drug will be available at government’s price.

The decision has been taken in view of the increasing cases of black marketing of Remdesivir.

“There was a shortage of Remdesivir injection. Because of this, incidents of black marketing took place, several people lost their lives as they have not received Remdesivir, so we decided to increase its production. But we tried (and to got manufacturing rights), Remdesivir will be provided to people at government’s price. Now, I think there will be no black marketing or no person will die due to lack of it, there is no reservation, can be provided to other states when there will be surplus,” Gadkari said.

May 7, 2021 0 comment