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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 Mankhurd Shivaji Nagar bridge should be opened for weighing vehicles: Abu Asim Azmi

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abu aasim aazmi

Mumbai: Maharashtra Samajwadi Party leader and MLA has demanded in the assembly that a flyover bridge should be started for heavy vehicles to curb fatal accidents in Mankhurd Shivaji Nagar. Fatal accidents are happening every month in Mankhurd Shivaji Nagar. Earlier there were high tension wires on the bridge built on GM Link Road, then the bridge was closed due to heavy vehicles. Later the wires were also removed and the flyover department has also allowed heavy vehicles to pass, however, heavy vehicles are still not being allowed to move. Today in the House, a demand was made to start the movement of heavy vehicles on this bridge. Abu Asim Azmi said that recently a tragic accident took place here in which three people died.

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Maharashtra

Wanted accused in Mumbai 1993 riots arrested after 32 years

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CRIME

Mumbai: Police have claimed to have arrested one of the most wanted accused involved in the 1993 Mumbai riots. Mumbai’s Wadala police arrested a fugitive accused who was on the run for 32 years during an operation to search for wanted accused. 54-year-old Arif Ali Hashimullah Khan has been arrested from Antop Hill. The accused did not appear in court during the hearing. A warrant was also issued against him, after which the police arrested the accused and presented him in the court and the court ordered his remand. This operation was carried out by Mumbai Police Commissioner Deven Bharti and Port Zone DCP Vijay Sagar.

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Maharashtra

Sashil Kodiyeri apologizes after tension over Marathi-Hindi controversy

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Maharashtra: In the context of the Mumbai Marathi-Hindi controversy, Shishil Kodia has apologized for his controversial statement. He said that his tweet was misrepresented. I am not against Marathi. I have been living in Mumbai and Maharashtra for the last 30 years. I am a fan of Raj Thackeray. I constantly comment positively on Raj Thackeray’s tweets. I tweeted in my emotions and I made a mistake. This tense and tense atmosphere should end. We need a favorable environment to accept Marathi. So I request you to forgive me for this mistake for Marathi. Earlier, Shishil Kodia had made a controversial statement about Marathi and refused to speak Marathi, due to which MNS workers attacked and pelted stones at Shishil’s company WeWork. After which Shishil has now apologized to X

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