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Monday, October 3, 2022

COVID-19: Antiviral therapeutic arsenal rich

Vaccines against COVID-19 have proven to be effective in reducing disease severity and transmission of infection. However, vaccination faced several challenges, highlighting the need for the discovery and design of antiviral drugs that can strengthen the therapeutic arsenal against COVID-19.

March 11, 2020 is a turning point for humanity in terms of public health. On this date, the Director-General of the World Health Organization (WHO), Tedros Adhanom Ghebreyesus, declared that COVID-19 may indeed qualify as a pandemic. Humanity has thus found itself at the beginning of a new era that puts health at the center of a common future. The Center for Systems Science and Engineering at Johns Hopkins University in Baltimore, United States, counts as of August 15, 2022, despite stringent health and policing measures imposed by governments around the world to prevent the spread of SARS-CoV-2 Gaya has 591,312,406 confirmed cases of Covid-19 worldwide and 6,438,307 deaths, including 1,197,866 cases and 10,581 deaths in Lebanon.

The rapid development and mass production of messenger ribonucleic acid (or mRNA) vaccines has been instrumental in combating the devastating pandemic waves of COVID-19. However, the difficulties in accessing these vaccines remain, as the United Nations Refugee Agency points out, breakthrough infections (ie infections acquired despite a complete vaccination course and immune system being efficient) and crescendo accumulation of mutations by the virus allow emerging forms. Gives birth, sometimes called worrisome. These are all factors that can constitute an increased risk of re-infection and therefore possible contracting of severe forms of the disease.

absolute priority

Therefore the development of antiviral therapy has increasingly become a practical necessity, even an absolute priority for the treatment of an increasing number of patients. Furthermore, several proteins encoded by SARS-CoV-2 have been identified as promising molecular targets because of their essential roles in the viral life cycle. Indeed, the virus’s entry-mediated viral spike protein, called “spike” or S, binds to a receptor, called ACE2, which is present on the surface of host cells, particularly at the level of the lungs. Is. But also at the level of the heart, digestive system, kidneys, vessels and ENT area.

The ubiquitous expression of the said receptor would explain the diversity of symptoms listed in patients. Once the coronavirus is inside the cell, a set of enzymes take part in its replication. These include two proteases, enzymes required for the cleavage of proteins that participate in the synthesis of new viral particles, and RNA polymerase, a central enzyme in the process of viral transcription. Thus, protein S, some proteases and RNA polymerases represent preferred targets for the design and development of antiviral drugs against SARS-CoV-2. In addition, antivirals that have already received formal approval or emergency use authorization from the US Federal Food and Drug Administration (FDA) for the treatment of Covid-19 are inhibitors targeting these viral proteins.

medical arsenal

Over the past two years, several advances in antiviral treatments have strengthened the available therapeutic arsenal against COVID-19. Thus various strategies have been deployed on the scientific front in the search for antiviral molecules against Covid-19, such as re-evaluation of therapeutic molecules already approved or being tested beyond their original indications, high-throughput candidate molecules. But the purpose of screening is to accelerate future medicine. Search, says virtual screening in silico (i.e. performed using a computer) libraries of molecules and to predict essential properties (physicochemical or biological) of drug discovery based on the biochemical structure. At the start of the pandemic, drug repurposing, which involved testing a pharmaceutical molecule for the pathology for which it was initially developed, aroused great interest among researchers, prompting rapid identification of already approved drugs. Bet on. Indications and which would be potentially effective against Covid-19.

Eureka!

Remdesivir, initially developed to treat Ebola virus infection, was the first molecule to be active against SARS-CoV-2. Indeed, data from a clinical trial conducted on 1,062 patients (541 patients receiving remdesivir and 521 patients receiving placebo) and published by Beigel in May 2020. and others. In The New England Journal of Medicine ,NEJM) demonstrated superior efficacy of remdesivir compared to placebo in adults hospitalized in terms of recovery time, positive for COVID-19, and presenting symptoms of lower respiratory tract infection. However, this assessment was far from unanimous: the results of another essay, titled Solidarity, published in December 2020 NEJM, contradicted those of the first report. The WHO, which showed itself in favor of the use of remdesivir in June 2020, thus suggested that it should no longer be used, noting that the said molecule “has no significant effect on mortality, ventilation”. Mechanics required, timing of clinical improvement and other important patient outcomes”.

first authority

After the publication of the new data, in January 2022 Gottlieb. By and others. In NEJMWHO has updated its recommendation, now suggesting the use of remdesivir in adult patients with mild or moderate COVID-19 who are at high risk of hospitalization. The study was conducted on 562 non-hospitalized patients (279 patients receiving remdesivir and 283 patients receiving placebo) with at least one risk factor for disease progression (age over 60, obesity, or certain co-existing medical conditions).

Remdesivir thus became the first drug to receive marketing authorization by the FDA in the United States and the European Medicines Agency (EMA) in Europe to treat hospitalized patients with Covid-19. Meanwhile, on October 1, 2021, it was announced that mollupiravir, a drug originally designed to treat infection caused by the Venezuelan equine encephalitis virus (VEEV), was used in hospitalization in patients with mild or moderate Covid-19. Can significantly reduce the risk of being admitted or dying. ,

Interim analysis of Phase III randomized and multicentre clinical trials (conducted in multiple centers) showed that only 7.3% of patients in the mollupiravir group were hospitalized or died within 29 days of the start of treatment. whereas 14.1% of those patients had died. in the placebo group. Entitled MOVe-OUT, the trial involved 775 COVID-19 positive patients with one or more risk factors for disease progression. Bernard and others. Thus concluded that Molnupiravir can reduce the rate of death or hospitalization by about 50%.

On November 4, 2021, Molnupiravir was approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) to treat patients with a mild to moderate form of Covid-19. Thus it has become the first oral drug to be included in the treatment guidelines for COVID-19. A few weeks later, on December 23, 2021, it was the FDA’s turn to grant emergency use authorization for molunpiravir to treat high-risk adults with mild to moderate disease.

In addition to drug repurposing, new molecules, including neutralizing multiple monoclonal antibodies targeting the viral spike protein S and a specific protease inhibitor, have also been discovered, developed and approved by drug regulatory authorities. In the United States, Europe or elsewhere, as a Covid-19 treatment. This part will be the subject of a separate article on here beirut,

World Nation News Desk
World Nation News Deskhttps://worldnationnews.com/
World Nation News is a digital news portal website. Which provides important and latest breaking news updates to our audience in an effective and efficient ways, like world’s top stories, entertainment, sports, technology and much more news.
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