SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

Redondo, Natalia; Zaldívar‐López, Sara; Garrido, Juan J.; Montoya, María

doi:10.3389/fimmu.2021.708264

Cited by 258 publications

(294 citation statements)

References 67 publications

(78 reference statements)

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“…Downstream in the RNA are 11 accessory proteins encoded by ORFs, whose order is ORF3a, ORF3b, ORF3c, ORF3d, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c and ORF10, respectively [ 18 ]. They interact with four structural proteins, but their roles remain unknown [ 19 ]. The four structural proteins are spike surface glycoprotein (S), small envelope protein (E), membrane or matrix protein (M), and nucleocapsid protein (N) [ 20 ].…”

Section: Genome Structure Of Sars-cov-2 Virusmentioning

confidence: 99%

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

2021

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The World Health Organization reports that SARS-CoV-2 has infected over 220 million people and claimed over 4.7 million lives globally. While there are new effective vaccines, the differences in behavior of variants are causing challenges in vaccine development or treatment. Here, we discuss Delta, a variant of concern, and Lambda, a variant of interest. They demonstrate high infectivity and are less responsive to the immune response in vaccinated individuals. In this review, we briefly summarize the reason for infectivity and the severity of the novel variants. Delta and Lambda variants exhibit more changes in NSPs proteins and the S protein, compared to the original Wuhan strain. Lambda also has numerous amino acid substitutions in NSPs and S proteins, plus a deletion in the NTD of S protein, leading to partial escape from neutralizing antibodies (NAbs) in vaccinated individuals. We discuss the role of furin protease and the ACE2 receptor in virus infection, hotspot mutations in the S protein, the toxicity of the S protein and the increased pathogenicity of Delta and Lambda variants. We discuss future therapeutic strategies, including those based on high stability of epitopes, conservation of the N protein and the novel intracellular antibody receptor, tripartite-motif protein 21 (TRIM21) recognized by antibodies against the N protein.

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Section: Genome Structure Of Sars-cov-2 Virusmentioning

confidence: 99%

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

2021

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“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes COVID-19, is an enveloped RNA virus that belongs to the beta coronavirus [5]. SARS-CoV-2 is composed of four different structural proteins, including spike, envelope, membrane, and nucleocapsid protein [6]. Among these structural proteins, the spike protein has received the most attention, as it can induce potent immune responses and is a ligand for angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 [7,8].…”

Section: Introductionmentioning

confidence: 99%

Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells

Kim

Jeon

Kim

et al. 2021

Viruses

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.

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“…2A and S2A). ORF7a encodes a SARS-CoV-2 accessory protein, a putative type-I transmembrane protein involved in antagonizing the type I IFN response (reviewed in (19)). The reads mapping to the ORF7a sequence are approximately 20 nt-long (Fig.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

Pawlica

Yario

White

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), continues to be a pressing health concern. In this study, we investigated the impact of SARS-CoV-2 infection on host microRNA (miRNA) populations in three human lung-derived cell lines, as well as in nasopharyngeal swabs from SARS-CoV-2 infected individuals. We did not detect any major and consistent differences in host miRNA levels after SARS-CoV-2 infection. However, we unexpectedly discovered a viral miRNA-like small RNA, named vmiR-5p (for viral miRNA), derived from the SARS-CoV-2 ORF7a transcript. Its abundance ranges from low to moderate as compared to host miRNAs. vmiR-5p functionally associates with Argonaute proteins (core components of the RNA interference pathway) leading to downregulation of host transcripts. One such host messenger RNA encodes Basic Leucine Zipper ATF-Like Transcription Factor 2 (BATF2), which is linked to interferon signaling. We demonstrate that vmiR-5p production relies on cellular machinery, yet is independent of Drosha protein, and is enhanced by the presence of a strong and evolutionarily conserved hairpin formed within the ORF7a sequence.

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SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

Cited by 258 publications

References 67 publications

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19

Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells

SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes

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