Current Pharmaceutical Design - Volume 27, Issue 32, 2021

In order to treat severe acute respiratory syndrome coronavirus (SARS-CoV), till now, no such specific treatment is available. Various coronaviruses (CoV) such as SARS-CoV, MERS-CoV (Middle East Respiratory Syndrome), and SARS-CoV-2 can infect humans and the name was implicated due to their crown shape. SARS-CoV-2 is also called COVID-19 which was found to be a novel strain of coronavirus and is transmitted primarily through small droplets of viral particles that target the human body through the open pathways. Researchers have observed that microbes can survive for a longer duration as they get adhered to any object or surface. Nanoparticles have the capability to disable these pathogens even before they enter the body. To eradicate conventional time consuming steps like quantitative real-time polymerase chain reaction for detection of COVID-19, nanoparticles mediated sensing approaches provide great advances in rapid diagnosis. Nanoparticles- based biosensors are comparatively beneficial which offer tremendous potential for rapid medical diagnosis. Nanotechnology can be refined and optimized to attack a wide variety of pathogens. As compared to other large molecular structures, nanoparticles being small in size, have high sensitivity for bio-sensing and can move throughout the body without disruption of the immune function.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for the coronavirus disease- 2019 (COVID-19) pandemic, which was first reported from Wuhan, China, in late 2019. This infection spread to thousands of people globally within a short span of time with a progressive trend to mortality of citizens. Posing a potential public health threat, SARS-CoV-2 progressed from animal-to-human to human-tohuman transmission with symptoms ranging from little or no illness to persons being severely ill and many deaths, confirming two criteria for declaring COVID-19 a pandemic. The disease shows a progressive trend in symptomology, ranging from mild to severe pneumoniae to respiratory and multi-visceral failure that often leads to the death of patients with comorbidity within a short span of time. Intensive research efforts on different aspects of this human pathogen are underway across the globe for elucidating viral transmission routes and the mechanisms employed to overcome host defense responses. Due to the massive infective potential, studies are being carried out to develop effective diagnostics and therapeutic interventions, including re-purposing antivirals and other potential inhibitors. Herein, we describe the taxonomic classification of 'SARS-CoV-2', the structural organization of its genome, its infectivity, transmission, and receptor interaction; and we summarize risk assessment and approaches used for prevention of the infection. Finally, we discuss important aspects of the development of diagnostic tools and therapeutic countermeasures that have the potential to help in controlling the COVID-19 pandemic.

Background: Viruses are known as the major causative agents for infectious diseases globally. The coronaviruses are one of the serious pathogens to cause serious diseases in humans. Recently identified SARSCoV- 2 from Wuhan City, China, has emerged as a serious threat to human health and caused a global pandemic. Bats have been confirmed as a primary source of infection. The vaccination of the human population and animals serving as a potential reservoir is a straightforward strategy to control the transmission of any pathogen to humans. Natural products from many herbal plants are well known to have novel antiviral properties and evaluated against various viral diseases. There are many alkaloids that have shown to be effective against coronaviruses. Methods: Recently, the antiviral efficacy of natural alkaloids known as Homoharringtonine (HTT) and Emetine has been evaluated and provided promising results against coronaviruses, including SARS-CoVs. These alkaloids may be very useful and can be used as antivirals against SARS-CoV-2 because they have already been reported to inhibit the replication of SASRS-CoV and other viruses in cell lines. Conclusion: This review specifically focuses on the recent findings of these alkaloids against coronaviruses and possible treatment options for SARS-CoV-2. It is expected that natural products as alkaloids from herbal plants could be considered as novel and valuable candidates for the new antiviral drugs against SARS-CoV-2.

In 2019, a new virus -SARS-COV2 possibly emerged in China, which infected many people affecting mainly the respiratory system. SARS-COV2 gets transmitted by inhalation of droplets from the infected persons. Symptoms start to appear after the incubation period of the virus which ranges from 2 to 14 days. In most people, symptoms are usually mild such as fever, sore throat, cough, chest tightness and fatigue. In other people, the disease might progress into severe pneumonia leading to several fatal consequences. Treatment is usually supportive and the role of antiviral is not established yet. Home isolation for mild cases is important for the prevention of the transmission of infection. Although the rate of transmission of this virus is faster than other viruses from the family, such as MERS-CoV, it has a lower fatality rate. The main difference in the genome structure of this family, which makes it distinguishable from other viruses is its use of (+) ssRNA as genetic material, which comprise 5’ cap located at one end and 3' polyadenylation tract at the other end. During infection of an exposed host cell, viral-encoded protease cleaves the polyprotein that results from translation of 5’ open reading frame (ORF) of the genome, culminating in the release of multiple nonstructural proteins such as helicase (Hel), adenosine triphosphate (ATPase) and RNA-dependent RNA polymerase (Rep). These proteins are responsible for the replication process in addition to the syntheses of the sub genomic mRNA used as transcription template strand. In this review article, we discussed the transmission pathways, genetic sequence and current treatment approach of COVID-19.

Background: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (M^pro) play a significant role in infection development were considered as potential drug targets. Methods: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke’s Phytochemical and Ethnobotanical Database, were docked with M^pro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR). Results: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and M^pro of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against M^pro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces. Conclusion: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.

Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of M^pro and SP of SARS-CoV-2. Methods: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs, were docked with M^pro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME properties, followed by docking with SP (PDB IDs: 6LXT and 6W41). Results: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: - 10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85 kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging results. Fiboflavin, an immunity booster, was found to inhibit both the M^pro and spike protein of SARSCoV- 2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303, and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals forces. Conclusion: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental validation and clinical trials.

Background: The unusual pneumonia outbreak that originated in the city of Wuhan, China in December 2019 was found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19. Methods: In this work, we have performed an in silico design and prediction of potential siRNAs based on genetic diversity and recombination patterns, targeting various genes of SARS-CoV-2 for antiviral therapeutics. We performed extensive sequence analysis to analyze the genetic diversity and phylogenetic relationships, and to identify the possible source of virus reservoirs and recombination patterns, and the evolution of the virus as well as we designed the siRNAs which can be used as antivirals against SARS-CoV-2. Results: The sequence analysis and phylogenetic relationships indicated high sequence identity and closed clusters with many types of coronavirus. In our analysis, the full-genome of SARS-CoV-2 showed the highest sequence (nucleotide) identity with SARS-bat-ZC45 (87.7%). The overall sequence identity ranged from 74.3% to 87.7% with selected SARS viruses. The recombination analysis indicated the bat SARS virus is a potential recombinant and serves as a major and minor parent. We have predicted 442 siRNAs and finally selected only 19 functional, and potential siRNAs. Conclusion: The siRNAs were predicted and selected based on their greater potency and specificity. The predicted siRNAs need to be validated experimentally for their effective binding and antiviral activity.