Can we Succeed in the Fight Against SARS-CoV-2 with its Emerging New Variants?

In 2019, the whole world came together to confront a life-threatening virus named SARS-CoV-2, causing COVID-19 illness. The virus infected the human host by attaching to the ACE2 and CD147 receptors in some human cells, resulting in cytokine storm and death. The new variants of the virus that caused concern are Alpha, Beta, Gamma, Delta, and Epsilon, according to the WHO label. However, Pango lineages designated them as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.429. Variants may be progressively formed in one chronic COVID-19 patient and transmitted to others. They show some differences in cellular and molecular mechanisms. Mutations in the receptor-binding domain (RBD) and N-terminal domain (NTD) lead to alterations in the host's physiological responses. They show significantly higher transmissibility rates and viral load while evading neutralizing antibodies at different rates. These effects are through mutations, deletion, and conformational alterations in the virus, resulting in the enhanced affinity of RBD to PD of ACE2 protein, virus entry, and spike conformational change. In the clinical laboratory, new variants may diagnose from other variants using specific primers for RBD or NTD. There are some controversial findings regarding the efficacy of the developed vaccines against the new variants. This research aimed to discuss the cellular and molecular mechanisms beyond COVID-19 pathogenesis, focusing on the new variants. We glanced at why the mutations and the ability to transmit the virus increase and how likely the available vaccines will be effective against these variants.

The World Against Versatile SARS-Cov-2 Nanomachines: Mythological or Reality?

Nanomachines hold promise for the next generation of emerging technology; however, nanomachines are not a new concept. Viruses, nature's nanomachines, have already existed for thousands of years. In 2019, the whole world had to come together to confront a life-threatening nanomachine named "SARS-CoV-2", which causes COVID-19 illness. SARS-CoV-2, a smart nanomachine, attaches itself to the ACE2 and CD147 receptors present on the cell surfaces of the lungs, kidneys, heart, brain, intestines, testes, etc. and triggers pathogenesis. Cell entry triggers a cascade of inflammatory responses resulting in tissue damage, with the worst affected cases leading to death. SARS-CoV-2 influences several receptors and signalling pathways; therefore, finding a biomaterial that caps these signalling pathways and ligand sites is of interest. This research aimed to compare the similarities and differences between COVID-19 and its elderly sisters, MERS and SARS. Furthermore, we glanced at emerging therapeutics that carry potential in eliminating SARS-CoV-2, and the tissue damage it causes. Simple prophylactic and therapeutic strategies for the treatment of COVID- 19 infection have been put forward.

The role of nanotechnology in current COVID-19 outbreak.

COVID-19 has recently become one of the most challenging pandemics of the last century with deadly outcomes and a high rate of reproduction number. It emphasizes the critical need for the designing of efficient vaccines to prevent virus infection, early and fast diagnosis by the high sensitivity and selectivity diagnostic kits, and effective antiviral and protective therapeutics to decline and eliminate the viral load and side effects derived from tissue damages. Therefore, non-toxic antiviral nanoparticles (NPs) have been under development for clinical application to prevent and treat COVID-19. NPs showed great promise to provide nano vaccines against viral infections. Here, we discuss the potentials of NPs that may be applied as a drug itself or as a platform for the aim of drug and vaccine repurposing and development. Meanwhile, the advanced strategies based on NPs to detect viruses will be described with the goal of encouraging scientists to design effective and cost-benefit nanoplatforms for prevention, diagnosis, and treatment.

COVID-19 Vaccines in Clinical Trials and their Mode of Action for Immunity against the Virus.

For nearly two decades, coronaviruses have caused many health and economic problems, while no effective commercial vaccine has yet been developed. It is worth mentioning that despite some mutations and recombination in SARS-CoV-2, its genotype is very close to the original strain from Wuhan, China. Therefore, the development of an effective vaccine would be promising. It might be hypothesized that BCG vaccination is performed in high-risk populations before the commercialization of an effective SARS-CoV-2 vaccine. However, the development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people's lives and long-term side effects must be considered. To this end, targeting of the receptor-binding domain (RBD) in spike and not whole spike, glycolization of FC receptors, PD-1 blockers, CPPs, etc., are promising. Therefore, the subunit vaccines or RNA vaccines that encode the RBP segment of the spike are of interest. To enhance the vaccine efficacy, its co-delivery with an adjuvant has been recommended. Nanoparticles modulate immune response with higher efficiency than the soluble form of antigens and can be functionalized with the positively charged moieties and ligands of targeted cells, such as dendritic cells, to increase cellular uptake of the antigens and their presentation on the surface of immune cells. This research aimed to discuss the COVID-19 vaccines entering the clinical trial and their mode of action effective immunity against the virus and discusses their advantages compared to each other.