Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases

Abstract

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

Keywords: COVID-19; Non-structural proteins; SARS-CoV-2; Structural proteins; Vaccine.

Fig. 1

SARS-CoV-2 entry receptors (ACE2, Eph, NRP-1, and CD147). Life cycle and role of proteins in replication of SARS-CoV-2

Fig. 2

Schematic illustration of proteomics studies, clinical and laboratory signs of people infected by SARS-CoV-2, SARS-CoV-2 receptors, and cytokines expression traits in different organs infected by SARS-CoV-2. The schematic illustrations of organs are obtained from Servier Medical ART: SMART [–94]

Fig. 3

SARS-CoV-2 may have a role in cancer or other diseases by using Eph receptors as entrance receptors and activating Eph receptor downstream signaling in the host cell (especially in malignant cells). Reprinted with permission from ref. [74]. Copyright 2022, Springer Nature

Fig. 4

The transmembrane protease serine subclass 2 (TMPRSS2), neuropilin-1 (NRP-1), ACE2, Eph receptors, ephrin ligands, P2X7, and CD147 are expressed on cells of the CNS as SARS-CoV-2 spike protein entrance receptors. JAK inhibitors can target ACE2, EphA/B receptors, and IL-6 receptors-activated signal transduction (JAKinibs). Also, the NLRP3 inflammasome can release IL-1 and IL-18 in response to ACE2, EphA/B receptors, TMPRSS2, NRP-1, P2X7, and CD147. These molecules may be targeted by IL-1 and IL-18 monoclonal antibodies, antagonists, and inflammasome inhibitors. Reprinted with permission from ref. [73]. Copyright 2022, Springer Nature

Fig. 5

(a) A compound known as a “lectibody” is created when the IgG crystallizable Fc and lectin of an antibody are combined. (b) Through the actions of CDC, ADCC, and ADCP, lectibodies’ lectins bind to surface glycoproteins, neutralizing viruses or infected cells and assisting the innate and adaptive immune systems in combating pathogens. Reprinted with permission from ref. [138]. Copyright 2022, Springer Nature

Fig. 6

The potential contribution of SARS-CoV-2 ORF8, NSP3, and NSP6 to cancer growth, chemoresistance, and tumor recurrence in infected cells (cancer cells). Reprinted with permission from ref. [248]. Copyright 2022, Springer Nature

Fig. 7

Intracellular signaling pathways stimulated by SARS-CoV-2 and the interactions of NSPs and ORFs with them