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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

Opposition protests against the government for declaring Wari as urban Naxal

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Mumbai: On the fourth day in the Maharashtra Legislative Assembly, the opposition created a ruckus over declaring Wari as urban Naxal and has made serious allegations against the government of insulting Wari. On the fourth day of the Maharashtra Legislative Assembly, the opposition has made several serious allegations against the ministers of the government while protesting on the steps of the Vidhan Bhavan. The ministers included in the cabinet of the state government are misusing their powers and occupying government lands in the state.

Just as the ruling front is trying to defame the holy pilgrimage of Hinduism, Wari, by calling Vitthurai and Warkars urban Naxalites and urban Maoists, in the same way it is insulting Wari Palkhi. This is reprehensible. Members of the Maha Vikas Aghadi staged a strong protest on the steps of the Vidhan Bhavan against the ruling front and accused the government of insulting Wari. In this demonstration, the members also raised slogans cursing the government and said that due to the scamster government, farmers are dying of hunger and the ministers are calling the laborers urban Naxalites. Shiv Sena leader of opposition Ambadas Danve, Vijay Varditwar, Sachin Ahir, Jitendra Ahawat etc. participated in this protest.

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Maharashtra

Maharashtra Urdu Academy should be formed, funds and staff should be appointed for the promotion of Urdu language Abu Asim Azmi

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Mumbai: Mumbai Maharashtra Legislative Assembly member Abu Asim Azmi has demanded the immediate formation of Urdu Academy to promote Urdu. He said that academies of other languages ​​including Gujarati and Marathi are active, but the condition of Urdu Academy is pathetic. Earlier there were 25 employees in this academy, but now only the superintendent is left. The remaining 24 have retired. The government needs to pay attention to the plight of Urdu.

The formation of this academy will promote Urdu. Azmi demanded that the Urdu Academy is facing difficulties due to the provision of funds. He said that the government allocates Rs 1 crore on paper, but this fund is not provided. Abu Asim Azmi said that Urdu is the language of our country. Whenever the Chief Minister or any other minister speaks in the House, they resort to Urdu poetry. But when it comes to the establishment of Urdu Academy and the development of Urdu language, the government is doing injustice

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Maharashtra

On the third day of Maharashtra Assembly, the opposition protested against the corruption of Rs 3000 crore.

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Mumbai: On the third day of Maharashtra Assembly in Mumbai, the opposition accused the ruling party of corruption and protested on the stairs of Vidhan Bhavan, accusing the government of giving contracts to every company of its choice. The state’s construction and development department has given a contract of Rs 3000 crore to Mahagathbandhan government’s Megha Engineering Company. Many shortcomings have been found in the work of this company, but despite this it is dear to the government. Therefore, slogans were raised on the stairs of Vidhan Bhavan that giving contract to this company is condemnable. Opposition members were also holding banner posters of contractor Megha Engineering, in which the picture of the owner of Megha Company was also visible. The opposition has intensified its protest against corruption in the Mahagathbandhan government. Shiv Sena opposition leader Ambadas Danve, Congress members and all parties including Congress protested loudly on the stairs of Vidhan Bhavan and drew the attention of the government towards this.

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