Emerging Molecular Prospective of SARS-CoV-2: Feasible Nanotechnology Based Detection and Inhibition

Abstract

The rapid dissemination of SARS-CoV-2 demonstrates how vulnerable it can make communities and is why it has attained the status of global pandemic. According to the estimation from Worldometer, the SARS-CoV-2 affected cases and deaths are exponentially increasing worldwide, marking the mortality rate as ∼3.8% with no probability of its cessation till now. Despite massive attempts and races among scientific communities in search of proper therapeutic options, the termination of this breakneck outbreak of COVID-19 has still not been made possible. Therefore, this review highlights the diverse molecular events induced by a viral infection, such as autophagy, unfolded protein response (UPR), and inflammasome, illustrating the intracellular cascades regulating viral replication inside the host cell. The SARS-CoV-2-mediated endoplasmic reticulum stress and apoptosis are also emphasized in the review. Additionally, host's immune response associated with SARS-CoV-2 infection, as well as the genetic and epigenetic changes, have been demonstrated, which altogether impart a better understanding of its epidemiology. Considering the drawbacks of available diagnostics and medications, herein we have presented the most sensitive nano-based biosensors for the rapid detection of viral components. Moreover, conceptualizing the viral-induced molecular changes inside its target cells, nano-based antiviral systems have also been proposed in this review.

Keywords: COVID-19; SARS-CoV-2 pathogenesis; autophagy; genetics and epigenetics; inflammasome; nanobased diagnosis; nanobased therapeutics.

FIGURE 1

Schematic representation of autophagy and UPR pathways as well as their interconnection in SARC-CoV-2 pathogenesis. Unfolded protein response (UPR), protein kinase R-like endoplasmic reticulum kinase (PERK), serine/threonine-protein kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) pathway, B-cell lymphoma 2(BCL2), Beclin 1 (BECN1), mechanistic target of rapamycin (MTOR), serine/threonine-specific protein kinase (AKT).

FIGURE 2

Nanotechnology-based detections of SARC-CoV-2 antigen or the whole virus. (A) (i) Multiple fragments of antisense-oligonucleotides against ORF1a/ORF1b/nsp3/nsp4/nsp5 functionalized on the surface of AuNPs. Antisense-oligonucleotides linked AuNPs binds with digested viral sample containing ORF1a/ORF1b/nsp3/nsp4/nsp5 genomic ssRNA, resulting in AuNPs aggregation which can be visualized spectrophotometrically as the color of solution changes from red to blue/purple. Inspired from Jacobi et al. (2020). (ii) Antibody against SARS-CoV-2 proteins such as S, E, and N protein and main proteinase (Mpro also called 3CLpro) functionalized on the surface of AuNPs will also aggregate after incubating digested viral sample containing SARS-CoV-2 proteins which can be visualized spectrophotometrically as the color of solution changes from red to blue/purple. Inspired from Jazayeri et al. (2018). (B) Screen-printed carbon electrode (SPCE) electrochemical biosensor strip can be designed against 2019-nCoV by exploiting the SARS-CoV-2 antibody immobilized onto the surfaces of carbon NPs (CNPs) through amide bonds formed between amino groups of CNPs and carboxylic groups of SARS-CoV-2 antibody. Inspired from Chowdhury et al., 2019.

FIGURE 3

Nanotechnology-based inhibition mechanisms of SARC-CoV-2. (A) Delivery of nuclear targeting TAT peptide tagged antisense siRNA against nsp3/4/5 or TAT peptide tagged nsp3/4/5 antisense oligonucleotide along with an antiviral drug through targeted organic antiviral nanosystem (TOAN) to SARS-CoV-2 infected goblet cell, resulting in activation of autophagy and viral inhibition. Inspired from Pan et al. (2012); Chen et al. (2018), Panigrahi et al. (2018), and Pala et al. (2019). (B) Delivery of antisense oligonucleotide against SARS-CoV-2 E gene through TOAN to SARS-CoV-2 infected goblet cell, resulting in viral E gene and arrest of NLRP3. Inspired from Nieto-Torres et al. (2015); Siu et al. (2019), and Conti et al. (2020). (C) Delivery of antioxidants (flavonoids) and antiviral drugs through TOAN to SARS-CoV-2 infected goblet cell, resulting viral entry inhibition and destruction with complimentary antioxidant effect to neutralize mitochondrial and endoplasmic reticulum stress. Outside the infected cell, antioxidant compounds could effectively bind viral S protein and prevent its entry into the cell. Inspired from Galluzzi et al. (2017); El-Hamid et al. (2018), and Jena et al. (2020).