SARS-CoV-2 coronavirus structure.
Insight into the function of the nucleocapsid protein could help develop drugs that lower coronavirus impact.
A multicenter partnership tracking the spread and evolution of the SARS-CoV-2 infection in Saudi Arabia has identified anomalies in the infections N protein related to increased viral loads in COVID-19 clients. The study supplies insight into the function of this nucleocapsid protein, which might assist establish drugs that lower the impact of coronavirus infection.
” The nucleocapsid (N) protein is the most plentiful protein in all coronaviruses, consisting of SARS-CoV-2,” describes KAUST research study scientist Muhammad Shuaib. This protein binds to different parts of the viral RNA, impacting how it is packaged within the infection. It also plays roles inside host cells associated with viral duplication and host immune responses.
Further tests in lab cells recommended that the modifications in the N protein allow the virus to more efficiently hijack host cell translation equipment to facilitate virus duplication.
The researchers, working with Arnab Pain, found that two successive anomalies in the N protein, called R203K and G204R, were connected with increased severity of COVID-19 in patients. Analyses revealed that the modifications 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
Additional tests in laboratory cells suggested that the changes in the N protein enable the virus to more efficiently pirate host cell translation machinery to assist in infection replication. They were also associated with increased expression of genes involved in interferon and chemokine production. This might be behind the lethal cytokine storm that happens in some COVID-19 clients, making it really hard for them to breathe.
The findings were the result of analyses of viral genome sequences from 892 client samples taken from various parts of Saudi Arabia between March and August 2020, fairly early in the pandemic. This was followed by contrasts with patient data to comprehend how anomalies impacted viral load and virulence.
” Compared to the spike protein, the N protein is extremely conserved in the different coronaviruses, like SARS and MERS; yet attempts to design vaccines versus it have actually not achieved success,” says Tobias Mourier, a consultant research scientist dealing with Pains group. “Understanding N proteins function might assist develop drugs that target it and potentially limitation disease seriousness in COVID-19 and other coronavirus infections.”
The KAUST-led research study team, that includes researchers and clinicians from institutions and health centers all over Saudi Arabia, continues to monitor the SARS-CoV-2 infection across the country and observe how anomalies impact virus-host interactions under different vaccination routines. “Sequencing virus genomes and reporting genomic modifications from regions of the world that are significantly underrepresented in existing databases is essential for tracking and evaluating new variations of concern,” says Pain.
Recommendation: “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.
” The nucleocapsid (N) protein is the most abundant protein in all coronaviruses, consisting of SARS-CoV-2,” explains KAUST research study researcher Muhammad Shuaib. This protein binds to various parts of the viral RNA, impacting how it is packaged within the virus. It also plays functions inside host cells related to viral duplication and host immune actions.