Tag: SARS-CoV-2

  • IISc researchers provide alternative mechanism to render viruses like SARS-CoV-2 inactive

    By PTI

    BENGALURU: Researchers at the Indian Institute of Science have developed a new approach that provides an alternative mechanism to render viruses like SARS-CoV-2 inactive, according to IISc.

    In a study published in ‘Nature Chemical Biology, the researchers report the design of a new class of artificial peptides or mini proteins that can not only block virus entry into our cells but also clump virions (virus particles) together, reducing their ability to infect.

    A protein-protein interaction is often like that of a lock and a key, the Bengaluru-based IISc noted in a statement.

    This interaction can be hampered by a lab-made mini protein that mimics, competes with, and prevents the ‘key’ from binding to the ‘lock’, or vice versa.

    In the new study, the team has exploited this approach to design mini proteins that can bind to, and block the spike protein on the surface of the SARS-CoV-2 virus.

    This binding was further characterized extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods.

    These mini proteins are helical, hairpin-shaped peptides, each capable of pairing up with another of its kind, forming what is known as a dimer.

    Each dimeric ‘bundle’ presents two ‘faces’ to interact with two target molecules.

    The researchers hypothesized that the two faces would bind to two separate target proteins, locking all four in a complex and blocking the targets’ action.

    “But we needed proof of principle,” says Associate Professor in the Molecular Biophysics Unit (MBU), IISc, and the lead author of the study, Jayanta Chatterjee.

    The team decided to test their hypothesis by using one of the mini proteins called SIH-5 to target the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein in human cells.

    The S protein is a trimer, a complex of three identical polypeptides.

    Each polypeptide contains a Receptor Binding Domain (RBD) that binds to the ACE2 receptor on the host cell surface.

    This interaction facilitates viral entry into the cell.

    The SIH-5 mini protein was designed to block the binding of the RBD to human ACE2.

    When a SIH-5 dimer encountered an S protein, one of its faces bound tightly to one of the three RBDs on the S protein trimer, and the other face bound to an RBD from a different S protein.

    This ‘cross-linking’ allowed the mini protein to block both S proteins at the same time, the statement said.

    “Several monomers can block their targets,” says Chatterjee.

    “(But) cross-linking of S proteins blocks their action many times more effectively. This is called the avidity effect.”

    Under cryo-EM, the S proteins targeted by SIH-5 appeared to be attached head-to-head.

    “We expected to see a complex of one spike trimer with SIH-5 peptides. But I saw a structure that was much more elongated,” says Assistant Professor at MBU and one of the corresponding authors, Somnath Dutta.

    Dutta and the others realised that the spike proteins were being forced to form dimers and clumped into complexes with the mini protein.

    This type of clumping can simultaneously inactivate multiple spike proteins of the same virus and even multiple virus particles.

    “I have worked with antibodies raised against the spike protein before and observed them under a cryo-EM. But they never created dimers of the spikes,” says Dutta.

    The mini protein was also found to be thermostable, it can be stored for months at room temperature without deteriorating.

    The next step was to ask if SIH-5 would be useful for preventing COVID-19 infection.

    To answer this, the team first tested the mini protein for toxicity in mammalian cells in the lab and found it to be safe.

    Next, in experiments carried out in the lab of Raghavan Varadarajan, a Professor at MBU, hamsters were dosed with the mini protein, followed by exposure to SARS-CoV-2.

    These animals showed no weight loss and had greatly decreased viral load as well as much less cell damage in the lungs, compared to hamsters exposed only to the virus.

    The researchers believe that with minor modifications and peptide engineering, this lab-made mini protein could inhibit other protein-protein interactions as well.

  • Indian-origin scientist among UBC researchers unveil world’s 1st molecular-level analysis of Omicron 

    By PTI

    TORONTO: A team of researchers, including an Indian-origin scientist at the prestigious University of British Columbia, has become the first in the world to conduct a molecular-level structural analysis of the Omicron spike protein, which could help accelerate the development of more effective treatments against the variant.

    Spike protein helps the virus enter and infect cells.

    Dr Sriram Subramaniam, professor in UBC faculty of medicine’s department of biochemistry and molecular biology, said that Omicron has greater binding affinity than the original SARS-CoV-2 virus, with levels more comparable to what seen with the Delta variant.

    The findings, published in the Science journal, sheds new light on why Omicron is highly transmissible and will help accelerate the development of more effective treatments, according to a statement issued by the Vancouver-based university.

    The analysis, done at near atomic resolution using a cryo-electron microscope, reveals how the heavily mutated variant infects human cells and is highly evasive of immunity, Subramaniam discussed the implications of his team’s research and underlined that  “vaccination remains our best defence against the Omicron variant”.

    The findings show strong antibody evasion and binding with human cells that contribute to increased transmissibility, and that vaccination remains the best defence, the university said.

    “UBC researchers are the first in the world to conduct a molecular-level structural analysis of the Omicron variant spike protein,” it said.

    Subramaniam said: “the Omicron variant is unprecedented for having 37 spike protein mutations, that’s three to five times more mutations than any other variant we’ve seen.”

    This is important for two reasons. Firstly, because the spike protein is how the virus attaches to and infects human cells. Secondly, because antibodies attach to the spike protein in order to neutralise the virus, he said.

    “Therefore, small mutations on the spike protein have potentially big implications for how the virus is transmitted, how our body fights it off, and the effectiveness of treatments. Our study used cryo-electron microscopy and other tests to understand how mutations impact the behaviour of the Omicron variant at a molecular level,” Subramaniam said.

    He said that several mutations (R493, S496 and R498) create new salt bridges and hydrogen bonds between the spike protein and the human cell receptor known as ACE2.

    This appears to increase binding affinity, how strongly the virus attaches to human cells, while other mutations (K417N) decrease the strength of this bond, Subramaniam said.

    He said it is remarkable that the Omicron variant evolved to retain its ability to bind with human cells efficiently despite such extensive mutations.

    “Our experiments confirm what we’re seeing in the real world, that the Omicron spike protein is far better than other variants at evading monoclonal antibodies that are commonly used as treatments, as well as at evading the immunity produced by both vaccines and natural infection,” he said.

    Notably, Omicron was less evasive of the immunity created by vaccines, compared to immunity stemming from natural infection in unvaccinated COVID-19 patients, he said.

    Both the characteristics seen as a result of spike protein mutations, strong binding with human cells and increased antibody evasion, are likely contributing factors to the increased transmissibility of the Omicron variant, he said.

    These are the underlying mechanisms fuelling the variant’s rapid spread and why Omicron could become the dominant variant of SARS-CoV-2 very quickly, he said.

    “The good news is that knowing the molecular structure of the spike protein will allow us to develop more effective treatments against Omicron and related variants in the future.

    Understanding how the virus attaches to and infects human cells means we can develop treatments that disrupt that process and neutralise the virus.

    “An important focus for our team is to understand better the binding of neutralising antibodies and treatments that will be effective across the entire range of variants, and how those can be used to develop variant-resistant treatments,” Subramaniam added.

    Omicron was first identified in South Africa and Botswana in November and is driving the current wave of infections.

  • Eight new cases of Omicron found in Maharashtra; none had history of overseas travel

    By PTI

    MUMBAI: Eight new cases of the Omicron variant of coronavirus were reported in Maharashtra – seven of them in Mumbai – and none of the patients had a history of international travel, the state health department said on Tuesday.

    With the fresh cases, which included three women, the tally of those infected with the newly discovered variant of SARS-CoV-2, the virus which causes COVID-19, rose to 28 in the state, the health department said in a bulletin.

    “As per the report given by the (Pune-based) National Institute of Virology today, 8 more patients were found to be infected with Omicron in the state. Out of these, seven patients are from Mumbai and one patient is from Vasai-Virar (a satellite township of Mumbai),” the health bulletin said.

    ​ALSO READ | COVID Task Force chief V K Paul pitches for quickly adaptable vaccine platforms

    Seven of these eight persons were vaccinated against coronavirus and their swab samples were taken for testing in the first week of December, it said.

    All of them – five men and three women – are in the age group of 24 to 41, the department said.

    It said of the eight, three are asymptomatic, while five have mild symptoms of the viral infection.

    “According to preliminary information, none of them have a history of international travel,” the bulletin said.

    ALSO READ | Pfizer confirms COVID pill’s results, potency versus omicron

    The bulletin said one of those who have been infected with Omicron had travelled to Bengaluru, while the others had visited New Delhi.

    Out of the eight patients, two are in hospital and six are in home isolation and their close contacts are being tracked, it added.

    Giving the break-up of 28 patients detected with Omicron so far, the bulletin said 12 are from Mumbai, 10 from Pimpri-Chinchwad (an industrial township in Pune district), two from Pune city, one each from Kalyan-Dombivali, Nagpur, Latur and Vasai-Virar.

    ​ALSO READ | WHO expects increase in number of deaths, hospitalisations from COVID variant Omicron

    “Out of these, nine patients have been discharged after returning negative RT-PCR test,” the health bulletin added.

    It said as many as 91,320 international travellers have arrived in Maharashtra through Mumbai, Pune and Nagpur airports in the recent days.

    Of these, 13,615 were from ‘at-risk’ countries.

    The emergence of Omicron, classified as a ‘variant of concern’ by the WHO, has caused alarm among scientists and governments across the world.

  • Inactivated virus vaccine Covaxin has cellular immune memory to Covid for at least six months: NII

    Immunological memory is the ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously.

  • COVID-19: No case of SARS-CoV-2’s Lambda variant found in India yet, says Centre

    By PTI
    NEW DELHI: No case of the Lambda variant of SARS-CoV-2 has been found in India so far, the government said on Friday. Responding to a question at a press briefing, joint secretary in the health ministry, Lav Agarwal, said Indian SARS-CoV-2 Genomics Consortium (INSACOG) is closely monitoring the variant.

    “Lambda was the seventh variant of interest identified by the WHO (World Health Organisation) on June 14 and it has been detected in 25 countries,” he said.

    “In our country, no cases have been reported and INSACOG is monitoring it and we are watchful. In Peru, 80 per cent infections were from this variant. It has also been found in South American countries and also in the UK and European countries, and any public health impact will be monitored,” Agarwal said.

    NITI Aayog Member (Health) Dr VK Paul said the Lambda variant is a variant of interest so its total significance is still being explored. “As far as we know it has not entered our country, we have not detected this variant in our country. Our surveillance system INSACOG is very effective and it will detect it if it happens to enter our country because when you do sequencing, all this will be picked up. So we should watch for that,” he said.

    Paul said the Lambda strain is a variant of interest which means its public health significance is being watched but it has not been proven for excessive transmissibility, for impact on excess severity or any other public health issues like those related to vaccines.

    “We should be watchful for these variants because the virus is under pressure and when it goes under pressure then it tends to pick up characteristics that tend to help it in survival but as of now we should be watching such variants for their presence in our country but as of now we have no evidence that this has been detected in any part of our country,” he added.

  • Covaxin phase three results decoded: Vaccine offers 93.4 per cent protection from severe Covid, 65.2 per cent immunity against Delta variant

    Express News Service
    NEW DELHI: Covaxin has shown an overall efficacy of 77.8 % against symptomatic Covid19, 93. 4 % efficacy against severe disease and 65. 2 % efficacy against delta variant of SARS CoV 2, the results of its phase 3 clinical trials conducted on nearly 26,000 individuals have shown.  

    There had been massive pressure on Bharat Biotech, which has developed the vaccine with support from the ICMR, to release full data of the efficacy trials carried out earlier this year. Covaxin is the only fully homegrown Covid19 vaccine being used in India’s Covid 19 vaccination drive and it had received regulatory approvals before completing phase 3 trials in January. 

    Bharat Biotech has now released the full data from the late-stage trials of Covaxin, a whole inactivated virus-based vaccine, on the pre-print server medrxiv, which are based on accruing 130 confirmed Covid 19 cases, 106 in the placebo arm and 24 in the vaccine group.  

    “BBV152 (Covaxin) was immunogenic and highly efficacious against symptomatic and asymptomatic Covid19 variant associated disease, particularly against severe disease in adults,” the researchers associated with the company, ICMR and 25 sites where the trials were conducted and a US based independent consultancy firm said.

    “Vaccination was well tolerated with an overall incidence of adverse events observed over a 65 median of days that was lower than that observed with other Covid19 vaccines

    Importantly, said the study, the results also showed 63. 6 % effectiveness against asymptomatic cases, which experts said was crucial to cut down the community spread of Covid19 over a period of time.

    ALSO READ | Congress raises questions over Covaxin supply deal with Brazil, seeks probe

    “In my view, the most remarkable part of the study was division of the part in three groups, one of whom was followed for asymptomatic cases—something that most other mainstream vaccines had not done in their clinical trials,” said Rajeev Jayadevan, clinician, medical researcher and former president of the Indian Medical Association.

    It is particularly significant, he said, as it gives the assurance that those fully vaccinated, may be far less likely to be carrier of infections.

    “Such an assurance is helpful in workplaces among others and in the long run will curb the spread of the disease in the community as the percentage of vaccinated population grows,” added Jayadevan.

    The study meanwhile said that there were 16 cases who met the severe symptomatic Covid-19 cases definition and all but one of whom were in the placebo group, resulting in a vaccine efficacy of 93·4% against severe disease.

    There were 15 deaths in the study, none of which were considered by the investigators to be related to the vaccine or placebo; six deaths were reported to be related to Covid. In the vaccine recipients, there were five deaths all due to causes unrelated to vaccination-cerebellar haemorrhage, haemorrhagic stroke, ovarian cancer with metastasis, sudden cardiac death, and Covid19.

    Ten placebo recipients died, also from unrelated conditions: alcohol overdose, myocardial infarction, cardiac arrest with underlying hypertension, five from Covid 19 and two which remain to be determined.

    Overall, as per the analysis, incidence rates of adverse events were lower after the second dose than the first, and tended to be slightly higher in the vaccine group than the placebo group.

    “However, all incidence rates were low, with only 12·4% reporting any solicited adverse events,” the study said.

    In the study, a total of 79 variants were reported from 16,973 samples, 18 in the vaccine and 61 in the placebo group.

    ALSO READ | Covaxin Brazil pricing: Bharat Biotech denies receiving advance payments, supplying vaccines

    Among 50 delta (B.1.617.2) positive-confirmed cases, which is now the most dominant strain of SARS CoV2 in India, 13 and 37 participants were in the vaccine and placebo arms, resulting in vaccine efficacy of 65·2%.

    Significantly, in breakthrough symptomatic delta variant infections, based on Ct values, the viral load in the vaccine arm was significantly lower than the placebo arm, the analysis has said.

  • Delta variant was main circulating strain during second Covid wave in Chandigarh: PGIMER

    The director of the city-based premier medical institute, Jagat Ram, also advised people to adhere to Covid appropriate behaviour and opt for vaccination to break the infection #39;s chain of transmission

  • India, Sri Lanka to scale up the genome surveillance for SARS-CoV-2

    By Express News Service
    NEW DELHI: A consortium of researchers from India and Sri Lanka will work to scale up the genome surveillance for SARS-CoV-2 in the two countries with a network of satellite MicroLabs in tier 2 and tier 3 cities.

    The evolution of new and more transmissible variants of SARS-CoV-2, their faster spread and impact on the effectiveness of the approved diagnostic tests and vaccines against COVID-19, has been a big concern. These variants also pose a risk to the success of the global pandemic response efforts. 

    Funding for the researchers’ consortium led by CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB), India, and the University of Colombo, Sri Lanka is being provided by the Wellcome Trust. 

    ALSO READ | Now, India is 14th most charitable country, says World Giving Index 2021

    Researchers from India and Sri Lanka will leverage the funding to strengthen the genomic surveillance and epidemiology capacity in the two countries by setting up an integrated, scalable hub-and-spoke model of distributed clusters of sequencing.

    MicroLabs set up in tier 2 and tier 3 cities will be supported by the existing MegaLabs. 

    “This model will reduce the time from getting a positive test to sequence, as well as time from sequence to public data deposit. Such an outcome, in turn, will enable researchers to use the data for improving diagnostics, vaccines, and therapeutics and help relevant authorities to frame appropriate health policy decisions on time,” said the Office of the Principal Scientific Adviser to the Government of India. 

    The research consortium will also establish technical coordination with WHO-SEARO’s regional reference lab for genomic sequencing to streamline the terms of engagement and ensure overall synchronization. In addition, standardized lab skills and training curriculum would be designed to help build the capacity of researchers and partners in both countries.

    “I estimate that we can shave three weeks off current timelines by establishing large, high-throughput sequencing hubs, alongside smaller, distributed ‘spokes’ that perform rapid but low-throughput sequencing, and by improving logistics for integrating results from samples with clinical data,” wrote Dr Anurag Agrawal, Director, CSIR-IGIB in the Nature journal.

  • Samples sent for genome sequencing to identify new Covid-19 variant, says Maharashtra government

    By PTI
    PUNE: The Maharashtra government has sent a substantial number of samples from various districts for genome sequencing to verify if any new mutation of SARS-CoV-2 has taken place, with the aim being to identify new COVID-19 variant Delta Plus or AY.1, an official said here on Monday.

    The highly transmissible Delta variant of SARS-CoV-2 has mutated further to form the Delta Plus or AY.1 variant and it is said to be resistant to the monoclonal antibody cocktail treatment for COVID-19 recently authorized in India, he added.

    “We have sent substantial samples from various districts to investigate if there is any prevalence of Delta-plus ( or AY.1). The reports are expected to come by Tuesday,” said Dr.

    Pradip Awate, State Surveillance Officer.

    He said the state’s Directorate of Medical Education and Research (DMER) had signed an MOU with CSIR-Institute of Integrative and Genomic Biology (IGIB) under which BJ Medical here will be the nodal lab to perform genome sequencing of the samples.

    In its latest report on coronavirus variants, updated till last Friday, the health agency said Delta Plus was present in six genomes from India as of June 7.

    ALSO WATCH:

  • COVID: UK variant dominates North India, double mutant wrecking havoc in Maharashtra, Gujarat, Karnataka

    By PTI
    NEW DELHI: The UK strain of coronavirus is currently dominating parts of north India while double mutant could be found mostly in Maharashtra, Karnataka and Gujarat, Sujeet Singh, Director of National Centre for Disease Control (NCDC), has said.

    He, however, added that the B1.1.7 lineage of SARS CoV-2 (UK variant) is declining in proportion across the country in the last month and a half.

    Addressing a press briefing on Wednesday, Singh said the UK strain is dominating parts of north India including Punjab (482 samples) and Delhi (516), followed by Telangana (192), Maharashtra (83) and Karnataka (82).

    He said 10 top government laboratories and institutions have been sequencing the genomes of coronavirus since December.

    A total of 18,053 samples have been sequenced so far, he added.

    Singh said the information on genome sequencing has been shared with the states twice in February, four times in March and again four times in April.

    He said in the video-conferencing with states, the Health Ministry also informed about the current status of variants of concern and new mutants and stressed on increased and stringent public health interventions.

    The double mutant variant, also known as B.1.617, is mostly dominating Maharashtra (761), West Bengal (124), Delhi (107) and Gujarat (102), Singh said.

    The South African variant, also known as B.1.315, was predominantly found in Telangana and Delhi.

    Brazilian variant (P1) was only found in Maharashtra in a negligible proportion, he said.

    Singh said there is a frequent written communication on the variants by the Health Ministry and the NCDC to all states and UTs.

    He said states/UTs are advised to keep strict surveillance in the districts reporting new variants of concern where they can take up stringent public health measures including contact tracing, genome sequencing of positive samples of persons having history of international travel.

    Meanwhile, Maharashtra, Uttar Pradesh and Delhi are among 10 states that account for 72.19 per cent of the new COVID-19 cases reported in a day, the Union Health Ministry said on Thursday.

    New coronavirus cases and deaths in India hit a record daily high with 4,12,262 new infections and 3,980 fatalities being reported, taking the total tally of COVID-19 cases to 2,10,77,410 and the death toll to 2,30,168.

    The ministry said that Karnataka,Kerala, Haryana, West Bengal, Tamil Nadu, Andhra Pradesh and Rajasthan are among the other states in the list of 10.

    Maharashtra has reported the highest daily new cases at 57,640.

    It is followed by Karnataka with 50,112 while Kerala reported 41,953 new cases.

    Besides Maharashtra, Uttar Pradesh, Karnataka, Delhi, Chhattisgarh, Haryana, Punjab, Tamil Nadu, Rajasthan and Jhakhand account for 75.55 per cent of the new deaths.

    Maharashtra saw the maximum casualties (920).

    Uttar Pradesh follows with 353 daily deaths.

    “The National Mortality Rate has been falling and currently stands at 1.09 per cent,” the ministry said.

    India’s total active caseload has reached 35,66,398 and now comprises 16.92 per cent of the country’s total infections.

    A net incline of 79,169 cases recorded from the total active caseload in a span of  24 hours.

    Twelve states cumulatively account for 81.05 per cent of India’s total active cases, the ministry said.

    The cumulative number of COVID-19 vaccine doses administered in the country has crossed 16.25 crore.

    The ministry said 9,04,263 beneficiaries in the age group of 18-44 years received their first dose of COVID vaccine across 12 states and UTs.

    These states are Chhattisgarh (1,026), Delhi (1,29,096), Gujarat (1,96,860), Jammu and Kashmir (16,387), Haryana (1,23,484), Karnataka (5,328), Maharashtra (1,53,966), Odisha (21,031), Punjab (1,535), Rajasthan (1,80,242), Tamil Nadu (6,415) and UP (68,893).

    Cumulatively, 16,25,13,339 vaccine doses have been administered through 29,34,844 sessions, as per the provisional report till 7 am.

    These include 94,80,739 HCWs who have taken the first dose and 63,54,113 HCWs who have taken the second dose, 1,36,57,922 FLWs who have received the first dose and 74,25,592 FLWs who have taken the second dose and, 9,04,263 beneficiaries aged 18-44 who have taken the first dose.

    Besides, 5,31,16,901 and 1,29,15,354 beneficiaries more than 60 years old have been administered the first and second dose respectively while 5,38,15,026 and 48,43,429 beneficiaries aged 45 to 60 have taken the first and second dose.

    Maharashtra, Rajasthan, Gujarat, Uttar Pradesh, West Bengal, Karnataka, Madhya Pradesh, Kerala, Bihar and Andhra Pradesh account for 66.87 per cent of the cumulative doses given so far in the country, the ministry said.

    More than 19 lakh vaccination doses were administered in a span of 24 hours.

    As on Day-110 of the vaccination drive (May 5), 19,55,733 vaccine doses were given.

    Across 15,903 sessions, 8,99,163 beneficiaries were vaccinated for the first dose and 10,56,570 beneficiaries received their second dose of vaccine.

    India’s cumulative recoveries stand at 1,72,80,844 with 3,29,113 recoveries being registered in a day.

    Ten states account for 74.71 per cent of the new recoveries.