Why do SARS-CoV-2 NSPs rush to the ER?

Santerre, Maryline; Arjona, Sterling P.; Allen, Charles N. S.; Shcherbik, Natalia; Sawaya, Bassel E.

doi:10.1007/s00415-020-10197-8

Cited by 66 publications

(89 citation statements)

References 105 publications

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“…Coronaviruses, including SARS-CoV-2 that replicate in the cytoplasm compartmentalize their genome transcription in organelle-like structures thereby protecting the virus against host cell defenses and increasing the replication efficiency (Santerre et al 2020). We previously mapped the structural proteins of SARS-CoV-2 and demonstrated that the M protein the virus resembles the sugar transporter SemiSWEET (Thomas, 2020).…”

Section: Resultsmentioning

confidence: 99%

“…The nsps are critical elements of the replication and transcription complex (RTC), as well as immune system evasion. Through hijacking the endoplasmic reticulum (ER) membrane, nsps help the virus establish the RTC (Santerre et al 2020). The structure and function of nsps of SARS-CoV-2 is similar to SARS-CoV.…”

Section: Resultsmentioning

confidence: 99%

“…Nearly all RTC elements are encoded by the large replicase gene that consists of Orf1a and Orf1ab. The early formation of the RTC is an essential step in the SARS-CoV-2 life cycle to safeguard viral genome replication and to synthesize subgenomic mRNA (Santerre et al 2020). Until recently it was not understood how the newly synthesized genomes and messenger RNAs can travel from the sealed replication compartments to the cytosol to ensure their translation and the assembly of progeny virions.…”

Section: Discussionmentioning

confidence: 99%

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Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

Thomas¹

2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the disease COVID-19 has wreaked havoc on the health and economy of humanity. In addition, the disease is observed in domestic and wild animals. The disease has impacted directly and indirectly every corner of the planet. Currently, there are no vaccines and effective therapies for COVID-19. SARS-CoV-2 is an enveloped virus with a single-stranded RNA genome of 29.8 kb. More than two-thirds of the genome comprises Orf1ab encoding 16 non-structural proteins (nsps) followed by mRNAs encoding structural proteins, spike (S), envelop (E), membrane (M), and nucleocapsid (N). These genes are interspaced with several accessory genes (open reading frames [Orf] 3a, 3b, 6, 7a, 7b, 8, 9b, 9c and 10). The functions of these proteins are of particular interest for understanding the pathogenesis of SARS-CoV-2. Several of the nsps (nsp3, nsp4, nsp6) and Orf3a are transmembrane proteins involved in regulating the host immunity, modifying host cell organelles for viral replication and escape and hence considered drug targets. In this paper we report mapping the transmembrane structure of the non-structural proteins of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

Thomas¹

2020

Preprint

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“…Nsp3 (217 kDa; 1946 amino acids) produced by both pp1a and pp1ab, is the largest element of the replication and transcription complex (RTC) [ 35 ]. It contains multiple conserved domains that represent an N-terminal acidic phosphoesterase, a papain like protease (PLpro), Y-domain, transmembrane domain 1 (TM1) and an adenosine diphosphate-ribose 1′’-phosphatase (ADRP) (NCBI reference sequence YP_009725299) [ 2 ].…”

Section: The Non-structural Proteins Encoded By the Sars-cov-2 Genmentioning

confidence: 99%

Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

O’Leary

Dolly

Höschl

et al. 2020

IJMS

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An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E, M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.

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“…The remaining three restriction sites are cleaved by viral papain-like protease (PLpro, NSP3), which is also involved in the evasion of host antiviral immune responses [ 21 , 24 ]. Replication is initiated by the assembly of a replication/transcription complex (RTC), which concentrates the necessary NSPs in a microenvironment close to the viral RNA [ 25 ]. The central component of the RTC, formed by viral RNA-dependent RNA-polymerase (RdRp, NSP12) and its cofactors NSP7 and NSP8, has the capacity to generate full-length negative-strand RNA chains that serve as templates for the synthesis of positive-strand genomic (gRNA) and subgenomic (sgRNA) RNA [ 21 , 26 ] ( Figure 2 ).…”

Section: Sars-cov-2 Structure Infection Replication and Treatmenmentioning

confidence: 99%

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

2020

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The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment.

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Why do SARS-CoV-2 NSPs rush to the ER?

Cited by 66 publications

References 105 publications

Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

Mapping the Non-Structural Transmembrane Proteins of SARS-CoV-2

Unpacking Pandora from Its Box: Deciphering the Molecular Basis of the SARS-CoV-2 Coronavirus

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

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