SARS-CoV-2 coronavirus structure.
Insight into the function of the nucleocapsid protein could help develop drugs that reduce coronavirus impact.
A multicenter collaboration tracking the spread and evolution of the SARS-CoV-2Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name of the virus strain that causes coronavirus disease (COVID-19). Previous to this name being adopted, it was commonly referred to as the 2019 novel coronavirus (2019-nCoV), the Wuhan coronavirus, or the Wuhan virus.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>SARS-CoV-2 virus in Saudi Arabia has identified mutations in the virus’s N protein associated with increased viral loads in COVID-19First identified in 2019 in Wuhan, China, Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has spread globally, resulting in the 2019–20 coronavirus pandemic.” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>COVID-19 patients. The study provides insight into the function of this nucleocapsid protein, which could help develop drugs that reduce the impact of coronavirus infection.
“The nucleocapsid (N) protein is the most abundant protein in all coronaviruses, including SARS-CoV-2,” explains KAUST research scientist Muhammad Shuaib. This protein binds to various parts of the viral RNARibonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in coding, decoding, regulation and expression of genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. An RNA strand has a backbone made of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U), cytosine (C), or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]”>RNA, affecting how it is packaged within the virus. It also plays roles inside host cells related to viral replication and host immune responses.
The researchers, working with Arnab Pain, found that two consecutive mutations in the N protein, called R203K and G204R, were associated with increased severity of COVID-19 in patients. Analyses showed that the changes to the protein made it bind more strongly to the viral RNA.
From left: Sharif M. Hala, Sara Mfarrej, Professor Arnab Pain, Muhammad Shuaib and Tobias Mourier (not pictured) studied the N protein of SARS-CoV-2 to further understanding of its role in disease severity. Credit: © 2022 KAUST
Further tests in laboratory cells suggested that the changes in the N protein allow the virus to more efficiently hijack host cell translation machinery to facilitate virus replication. They were also associated with increased expression of genes involved in interferon and chemokine production. This could be behind the life-threatening cytokine storm that happens in some COVID-19 patients, making it very difficult for them to breathe.
The findings were the result of analyses of viral genome sequences from 892 patient samples taken from various parts of Saudi Arabia between March and August 2020, relatively early in the pandemic. This was followed by comparisons with patient data to understand how mutations affected viral load and virulence.
“Compared to the spike protein, the N protein is highly conserved in the different coronaviruses, like SARS and MERS; yet attempts to design vaccines against it have not been successful,” says Tobias Mourier, a consultant research scientist working on Pain’s team. “Understanding N protein’s function could help develop drugs that target it and potentially limit disease severity in COVID-19 and other coronavirus infections.”
The KAUST-led research team, which includes scientists and clinicians from institutions and hospitals all over Saudi Arabia, continues to monitor the SARS-CoV-2 virus nationwide and observe how mutations affect virus-host interactions under various vaccination regimens. “Sequencing virus genomes and reporting genomic changes from regions of the world that are severely underrepresented in current databases is essential for tracking and assessing new variants of concern,” says Pain.
Reference: “SARS-CoV-2 genomes from Saudi Arabia implicate nucleocapsid mutations in host response and increased viral load” by Tobias Mourier, Muhammad Shuaib, Sharif Hala, Sara Mfarrej, Fadwa Alofi, Raeece Naeem, Afrah Alsomali, David Jorgensen, Amit Kumar Subudhi, Fathia Ben Rached, Qingtian Guan, Rahul P. Salunke, Amanda Ooi, Luke Esau, Olga Douvropoulou, Raushan Nugmanova, Sadhasivam Perumal, Huoming Zhang, Issaac Rajan, Awad Al-Omari, Samer Salih, Abbas Shamsan, Abbas Al Mutair, Jumana Taha, Abdulaziz Alahmadi, Nashwa Khotani, Abdelrahman Alhamss, Ahmed Mahmoud, Khaled Alquthami, Abdullah Dageeg, Asim Khogeer, Anwar M. Hashem, Paula Moraga, Eric Volz, Naif Almontashiri and Arnab Pain, 1 February 2022, Nature Communications.
DOI: 10.1038/s41467-022-28287-8
Source: SciTechDaily
