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Scientists develop mechanism to inactivate Covid by blocking entry to cells

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 Scientists have developed a design of a new class of synthetic peptides that can not only block the entry of SARS-CoV-2 virus entry into cells but also clump the virions (virus particles) together, reducing their ability to infect.

Scientists at the Indian Institute of Science (IISc), in collaboration with researchers from the CSIR-Institute of Microbial Technology, have made use of this approach to design peptides that can bind to and block the spike protein on the surface of SARS-CoV-2 virus, said the Ministry of Science and Technology on Wednesday.

This binding was further characterised extensively by cryo-electron microscopy (cryo-EM) and other biophysical methods. This novel approach provides an alternative mechanism to render viruses like SARS-CoV-2 inactive, promising a new class of peptides as antivirals.

The research was supported under the Covid-19 IRPHA call of SERB Science and Engineering Research Board (SERB), a statutory body of Department of Science and Technology (DST).

The designed peptides are helical, hairpin-shaped, 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.

In the study published in Nature Chemical Biology, the researchers hypothesised that the two faces would bind to two separate target proteins locking all four in a complex and blocking the targets’ action. The team decided to test their hypothesis by using a peptide called SIH-5 to target the interaction between the Spike (S) protein of SARS-CoV-2 and ACE2 protein, the SARS-CoV-2 receptor 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 peptide 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 SIH-5 to block both S proteins at the same time. Under cryo-EM, the S proteins targeted by SIH-5 appeared to be attached head-to-head, and the spike proteins were being forced to form dimers.

Subsequently, the researchers showed that SIH-5 inactivated the viruses efficiently by cross-linking the spike proteins from different virus particles.

The team consisting of B Khatri, I Pramanick, SK Malladi, RS Rajmani, P Ghosh, N Sengupta, R Varadarajan, S Dutta and J Chatterjee from Indian Institute of Science (IISc), R Rahisuddin, S Kumar, N Kumar, S Kumaran and RP Ringe from CSIR-Institute of Microbial Technology, tested the peptide for toxicity in mammalian cells in the lab and found it to be safe.

When hamsters were dosed with the peptide and subsequently exposed to a high dose of SARS-CoV-2, they showed decreased viral load as well as much less cell damage in the lungs compared to hamsters exposed only to the virus, demonstrating the promise of this class of peptides as antivirals.

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

Maharashtra

Mumbai: Harassment of ordinary Muslims in the name of Bangladeshis should stop, Abu Asim makes serious allegations against the government over Home Minister Amit Shah’s statement

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abu azmi

Mumbai: Maharashtra Samajwadi Party leader Worker Assembly Abu Asim Azmi criticized the statement of Home Minister Amit Shah and said that it is the responsibility of the Home Minister and the Central Government to take action against Bangladeshi and Pakistani infiltrators. The population of Muslims in India has increased due to Bangladeshis. This is completely wrong. The residents of West Bengal and ordinary Muslims are being targeted under the guise of Bangladeshi and Pakistanis. He said that the government is yours in many states and at the center, so how do Bangladeshi infiltrators enter from the border? What action has the government taken against those who forge their documents so far? He said that targeting Muslims under the guise of Bangladeshi should be stopped, just as Karat Soumya is trying to fake the certificates and documents of every Muslim and is targeting Muslims. He said that the government should pay attention to how Bangladeshi infiltrators infiltrate from the Indian border. This is not the job of Congress, SP or other parties. It is the job of the government to take action against Bangladeshi and Pakistanis and to bring them to justice. But Muslims should not be harassed or disturbed. He said that action is being taken against those officers who are preparing documents for Bangladeshis.

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Mumbai Press Exclusive News

Crores of rupees were defrauded in the name of government jobs, the accused was arrested from Delhi… The accused had received money from hundreds of unemployed people

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Mumbai: The Mumbai Economic Wing has claimed to have arrested the accused in a case of cheating in the name of getting government jobs in the central and state governments in several districts of Maharashtra. Santosh Ganpat, a businessman from Navi Mumbai, filed a complaint that the accused Nilesh Kanshi Ram Rathore had charged him Rs 5 lakh for a government job and Rs 5 to 15 lakh for medical tests and appointment letters. The EOW has registered a case against him because he has cheated him of Rs 2.88 crore by promising him a job and during the investigation it was revealed that he has cheated him of Rs 10 crore. The Economic Wing has formed a team to arrest the absconding accused and searched him in Akola and other areas. The accused cheated hundreds of youths for recruitment in RCF in 2022. His complaint was filed with the EOW. The EOW received information that the accused was trying to escape from Delhi, on which the police arrested him from Delhi. The accused has been booked in Mumbai EOW and Pune Deccan. A criminal case has been registered and further investigation is underway. This operation has been carried out under the leadership of EOW chief Nisht Mishra.

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Mumbai Press Exclusive News

ANC action, drugs worth crores seized, 6 arrested

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Mumbai: The Anti-Narcotics Cell has claimed to have arrested six drug smugglers, including a Nigerian, including a Nigerian, including MD and Natropum tablets worth Rs 7.01 crore, during operations at various locations in Mumbai. 523 grams of cocaine, worth Rs 5.23 crore, was seized from a Nigerian in Vakola, Mumbai. Five accused were arrested in raids conducted in Ghatkopar, Kurla CST, Mazgaon, tardeo, Borivali areas, from whose possession Mephedone MD worth Rs 54.65 lakh was seized. These are part of five inter-state drug gangs. Other drugs including Natropum tablets were also seized in this operation. This operation was carried out by DCP Nunath Dhule on the instructions of the Mumbai Police Commissioner.

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