NSP16 2′-O-MTase in Coronavirus Pathogenesis: Possible Prevention and Treatments Strategies

Abstract

Several life-threatening viruses have recently appeared, including the coronavirus, infecting a variety of human and animal hosts and causing a range of diseases like human upper respiratory tract infections. They not only cause serious human and animal deaths, but also cause serious public health problems worldwide. Currently, seven species are known to infect humans, namely SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1. The coronavirus nonstructural protein 16 (NSP16) structure is similar to the 5′-end capping system of mRNA used by eukaryotic hosts and plays a vital role in evading host immunity response and protects the nascent viral mRNA from degradation. NSP16 is also well-conserved among related coronaviruses and requires its binding partner NSP10 to activate its enzymatic activity. With the continued threat of viral emergence highlighted by human coronaviruses and SARS-CoV-2, mutant strains continue to appear, affecting the highly conserved NSP16: this provides a possible therapeutic approach applicable to any novel coronavirus. To this end, current information on the 2′-O-MTase activity mechanism, the differences between NSP16 and NSP10 in human coronaviruses, and the current potential prevention and treatment strategies related to NSP16 are summarized in this review.

Interferon Control of Human Coronavirus Infection and Viral Evasion: Mechanistic Insights and Implications for Antiviral Drug and Vaccine Development

“…Mutant CoVs lacking 2ʹ– O methyltransferase activity were observed to be more vulnerable to antiviral action of IFN and IFIT than their wild-type counterparts [177] . Furthermore, attenuated vaccines with mutations at Nsp10 or/and Nsp16 have been developed due to the observation that targeting 2′-O-MTase activity will reduce viral proliferation and virulence [178] , [179] , [180] .…”

Structural biology of SARS-CoV-2: open the door for novel therapies

“…The Nsp16/Nsp10 complex in SARS-CoV-2 has high homology with those in other coronaviruses, and most residues that participate in catalysis and Cap/SAM binding are conserved. 307 , 312 Therefore, inhibitors that target this protein are promising candidates for development into broad-spectrum antiviral agents. Inhibitor design for Nsp16 can be viewed from multiple perspectives.…”

Recent insights into the structure and function of coronavirus ribonucleases

“…There is new structural evidence unveiling the protein interface of Nsp14 with the RTC, but how and if Nsp14 regulates the activity of this complex or how the complex may change Nsp14 exonuclease activity is unknown. Nsp10 is a cofactor for both the capping and exonuclease activity of Nsp14, yet Nsp10 is also critical for Nsp16 activity [ 93 , 94 ] using nearly the same interaction interface. The transfer of Nsp10 as the presumable limiting factor in capping is still under investigation.…”