Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV-2

ABSTRACTSevere Acute Respiratory Syndrome Coronavirus 2 is rapidly spreading around the world. There is no existing vaccine or proven drug to prevent infections and stop virus proliferation. Although this virus is similar to human and animal SARS- and MERS-CoVs the detailed information about SARS-CoV-2 proteins structures and functions is urgently needed to rapidly develop effective vaccines, antibodies and antivirals. We applied high-throughput protein production and structure determination pipeline at the Center for Structural Genomics of Infectious Diseases to produce SARS-CoV-2 proteins and structures. Here we report the high-resolution crystal structure of endoribonuclease Nsp15/NendoU from SARS-CoV-2 – a virus causing current world-wide epidemics. We compare this structure with previously reported models of Nsp15 from SARS and MERS coronaviruses.

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The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine

10.1101/2020.04.17.047498 ◽

2020 ◽

Cited By ~ 8

Author(s):

Monica Rosas-Lemus ◽

George Minasov ◽

Ludmilla Shuvalova ◽

Nicole L. Inniss ◽

Olga Kiryukhina ◽

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Keyword(s):

Crystal Structure ◽

Severe Acute Respiratory Syndrome ◽

Structural Genomics ◽

Immune Surveillance ◽

Healthcare Systems ◽

Viral Mrna ◽

Respiratory Complications ◽

Mrna Transcripts ◽

The World ◽

Respiratory Coronavirus

AbstractSARS-CoV-2 is a member of the coronaviridae family and is the etiological agent of the respiratory Coronavirus Disease 2019. The virus has spread rapidly around the world resulting in over two million cases and nearly 150,000 deaths as of April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 and SARS-CoV-2, respiratory complications derived from the infections have overwhelmed healthcare systems around the world. This virus is related to SARS-CoV-1, the virus that caused the 2002-2004 outbreak of Severe Acute Respiratory Syndrome. In January 2020, the Center for Structural Genomics of Infectious Diseases implemented a structural genomics pipeline to solve the structures of proteins essential for coronavirus replication-transcription. Here we show the first structure of the SARS-CoV-2 nsp10-nsp16 2’-O-methyltransferase complex with S-adenosylmethionine at a resolution of 1.80 Å. This heterodimer complex is essential for capping viral mRNA transcripts for efficient translation and to evade immune surveillance.

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The Role of High-Throughput Laboratories in Homeland Security

JALA Journal of the Association for Laboratory Automation ◽

10.1016/s1535-5535-03-00004-2 ◽

2003 ◽

Vol 8 (5) ◽

pp. 11-18

Author(s):

Tony J. Beugelsdijk ◽

Scott P. Layne

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Infectious Diseases ◽

Homeland Security ◽

High Throughput ◽

Biological Weapons ◽

The World ◽

Chemical And Biological Weapons ◽

Dangerous Place ◽

Terrorist Networks

Infectious diseases pose threats from natural and manmade sources, and arguably the situation is getting worse. The outbreak of the coronavirus causing the severe acute respiratory syndrome (SARS) shows that the world is linked by thousands of people traveling millions of miles every single day who can spread SARS or new strains of influenza with pandemic potential. 1 The world is also becoming a more dangerous place, with rogue nations and terrorist networks aggressively seeking nuclear, chemical, and biological weapons. Of these, biological weapons are the cheapest to produce and likely the most attractive because they can be used anonymously.

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