Experts expect ‘COVID’ to be resistant to antiviral drugs After vaccination and antibody immunization start to take away Preparing to develop a cocktail of second-generation antidote
The Medical Genome Center, Ramathibodi Hospital posted a Facebook page. Center for Medical Genomics disclose information New Omicron Avoid immunity from vaccines and antibodies to create immunity. and tend to be resistant to antiviral drugs as follows
Data from the World Health Organization shows that the death rate from COVID-19 The world is declining against the rate of COVID-19 infections. Increased new revenue around the world This indicates that infection prevention (with the vaccine) has decreased its effectiveness. while the treatment (with antiviral drugs) has better efficacy. The world has turned to rely on antiviral drugs as a second line of defense. But the problem that may be faced later is drug-resistant COVID (Figure 1).
The Genome Center develops a genome-wide transcription of the genetic code for COVID-19. Not only to follow up the new subspecies of Omicron in Thailand. But also to watch out for COVID with antiviral resistance genomes like 16 years ago that had to decode the genetic code of the HIV virus to modify antiviral drugs. to reduce the number of deaths from AIDS (Figure 0).
New species of Omicron Evade immunity from vaccines and drug resistance.antibody
It is now clear that emerging omicron substrains such as BA.2.75, BQ.1.1 and XBB can all evade immunity from booster vaccines. and natural immunity from infection Better than the original strain of COVID virus “Wuhan”
Researchers at the University of Texas have identified new COVID strains, Omicron’s ‘grandchildren’ BA.2, such as BA.2.75, and Omicron’s grandchildren, BA.5, such as BQ.1.1, as well as interspecific hybrids. Omicron family together, such as Omicron XBB (BJ.1XBA.2.75*)
Able to evade immunity from first-generation and second-generation vaccines 4 times more viral covid-19-bivalent-vaccine-boosters (using bivalent viruses as precursors/covid-19-bivalent-vaccine-boosters) than Omicron BA.5, enabling these new viruses to spread rapidly.
even found that the infected body The hybrid immunity created by natural infection after booster vaccination can slightly increase the protection against new strains of COVID-19 (Figure 2).
In addition, the emerging subspecies of Omicron are resistant to almost all “immunogenic antibody” drugs. (Picture 3)
An increase in the number of infected people was found
Notably, data from the World Health Organization indicate a marked increase in the number of new omicron infections worldwide. But the number of patients who have to be admitted to ICU and die from COVID-19 turned down significantly, the main reason is likely to be because
- Doctors and healthcare professionals have increased experience in treating COVID-19 (over the last 3 years) with antivirals and steroids. more systematically and standardized
- At this time, the COVID 2019 virus has not yet been found resistant. “antiviral pill” which is used orally to inhibit the multiplication of viruses within cells The inhibition of intracellular viral replication is not related to the viral spike protein gene. while all subspecies of Omicron are resistant to pre-immunized antibody injections Because the injected ready-made antibodies do not bind well to the virus spike proteins. As a result of mutations in the spiny protein gene, the spiny protein shape was rapidly changed from that of the original species (Figure 4).
Guidelines for treating COVID with antiviral drugs in Thailand
for Thailand bymedical department Ministry of Public Health together with a doctor specializing in the treatment of COVID-19 infection Both public and private sectors come together to formulate guidelines for medical practice, diagnosis, treatment, and prevention of COVID-19 infection in hospitals as a guideline for doctors across the country to make decisions about treating COVID-19 patients. -19 with Thai and foreign medicines Both in small children, older children, adults, pregnant women. Both antiviral pills and injections
with a selection method from andrographis paniculata, favipiravir (favipiravir), molnupiravir (Molnupiravir), Paxlovid (Paxlovid: nirmatrelvir/ritonavir), remdesivir (remdesivir), a combination long-acting antibody Used for prevention before exposure to the virus that causes COVID-19. (tixagevimab/cilgavimab (LAAB), and anti-inflammatory drugs (corticosteroid) (Figure 5).
Thai public health system Starting from the village health volunteers (VHVs) reaching people in every household in the manner of knocking on the door until arriving at the patient to receive treatment in the provincial hospital. should make Thai people have good access to antiretroviral drugs can reduce severe illness infections death
expected year 66 More antiretroviral drugs will be used.
It can be assessed that from 2023 onwards around the world including Thailand. There will be more anti-Covid-19 pills being used. Due to the mutation, ready-made vaccines and antibody drugs are ineffective in preventing infection. The problem is with widespread use of antiretroviral pills. Will it cause the virus to become resistant to antiviral drugs or not?
Medicines available in Thailand according to the medical practice guidelines of the Department of Medical Services. Ministry of Public Health (Figure 5) is
- Molenupiravir (Molnupiravir) should be started within 5 days of symptom onset.
- Remdesivir should be started within 5 days of the onset of symptoms.
- Paxlovid (nirmatrelvir/ritonavir) should be started within 5 days of symptom onset.
- Long-Acting AntiBody (LAAB): tixagevimab/cilgavimab It should begin within 7 days of the onset of symptoms.
Found resistance to antivirals??
The key question is
- Around the world, has the COVID-19 virus mutated into Molnupiravir resistant?
from current research data Molnupiravir has not been found to induce molnupiravir-resistant mutants. spread out (Figure 6).
- Around the world, has the COVID-19 virus mutated into remdesivir resistant?
Research data found that can induce remdesivir-resistant viruses in the laboratory But from the genetic code analysis of the entire genome of the corona virus 2019 from the world’s COVID database “”Gisaid (GISAID)”, more than 800,000 samples from people infected with COVID around the world. No remdesivir-resistant COVID-19 has yet been found (Figure 7).
- Around the world, have the COVID-19 virus mutated into resistance to Paxlovid?
The answer is that there is information from the research found that can induce the development of paxlovid-resistant viruses in the laboratory Stimulation-induced loci mutant in the laboratory Also found in the COVID-19 database, Gissade, but it has to wait for the isolation of those viruses to be tested in the laboratory to confirm whether they are resistant to antiviral drugs or not (Figure 8).
Experts around the world expect The virus is resistant to Paxlovid.
Paxlovid is highly effective in treating Contains nermatrelvir Will inhibit the function of the enzyme protease (protease inhibitor) of the virus from creating complete virus particles. Ritonavir slows down the breakdown of nermatrelvir. Makes the drug stay in the body longer
An independent study published in the New England Journal of Medicine found that Paxlovid reduced hospital stay time in vulnerable patients over 65 years of age. and reduced mortality by up to 79%, data from a hospital in Israel earlier this year (Figure 9) and from a study by the pharmaceutical company itself. Paxlovid has been found to reduce the risk of hospitalization and death by 88%.
Among the antiviral drugs for COVID-19 Paxlovid is highly effective in treating It is expected to become the main drug in the treatment of COVID-19. In the future, however, experts around the world believe that it will soon see COVID-19 spread. Resistance to paxlovid is certain to occur because current treatment is still on monotherapy. (monotherapy)
Like other RNA viruses, such as HIV, SARS-CoV-2 mutates over time, with drug resistance that is difficult to manage. In the past, HIV drug resistance persisted due to the use of only one type of drug to treat it. Drugs that block the activity of many HIV virus proteases In the past, there was a problem with drug-resistant bacteria quickly. as a single drug Until the simultaneous use of 2-3 antiretroviral drugs has been made, the problem of drug-resistant HIV has been solved since the 1990s to the present.
Developing a new antiviral drug 2 as a cocktail
taking many drugs at the same time or the introduction of several drugs packed together in one pill and eaten It’s like attacking and destroying many virus factories at once. causing the virus to be destroyed rapidly no chance of mutating resistance to antiretrovirals
Currently, the company that makes Paxlovid believes that The use of high drug concentrations and a short treatment period of only 5 days will reduce the likelihood of developing drug resistance. This gives the company time to develop a second-generation antiviral drug. It is expected that several drugs are mixed in the same tablet or capsule in a cocktail style.
What should I do to prevent the spread of the coronavirus? resistant to the antiretroviral drug Paxlovid
- First of all, Paxlovid should be used for prophylaxis. (prophylaxis) or not, because the more drugs are used, the faster resistance develops.
- Is it appropriate to use paxlovid in young, healthy people who are unlikely to become seriously ill?
A solution from the US Centers for Disease Control and Prevention (CDC) to reduce the use of PaxLovid among the population. Although Paxlovid is still recommended for early treatment of COVID-19, In infected people, symptoms are mild to moderate. Modified for use in vulnerable groups at high risk of severe disease progression. Earlier CDC criteria included adults and children under 12 (Figure 10).
We are fortunate to have antiretroviral drugs as one of the most effective tools to treat COVID. Therefore, it is necessary to use only as necessary to avoid drug resistance. We must stay ahead of the virus by rapidly developing new anti-coronavirus drugs. Especially drugs that have different mechanisms of action from the drugs that we currently have. To be used as anti-viral drugs in the form of a combination (of 2-3 drugs) using combination anti-viral drugs have been successfully used in the treatment of AIDS.
The Genome Center develops a genome-wide transcription of the genetic code for COVID-19. Not only to follow the emerging subspecies of Omicron. but also to monitor the antiviral resistance of the Coronavirus 2019 in Thailand
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