Current Pharmaceutical Design - Volume 27, Issue 9, 2021

Background: Coronavirus Disease-2019 belongs to the family of viruses which cause serious pneumonia along with fever, breathing issues and infection of lungs, and was first reported in China and later spread worldwide. Objective: Several studies and clinical trials have been conducted to identify potential drugs and vaccines for Coronavirus Disease-2019. The present study listed natural secondary metabolites identified from plant sources with antiviral properties and could be a safer and tolerable treatment for Coronavirus Disease-2019. Methods: A comprehensive search on the reported studies was conducted using different search engines such as Google Scholar, SciFinder, Sciencedirect, Medline PubMed, and Scopus for the collection of research articles based on plant-derived secondary metabolites, herbal extracts, and traditional medicine for coronavirus infections. Results: Status of COVID-19 worldwide and information of important molecular targets involved in COVID- 19 are described, and through literature search, it is highlighted that numerous plant species and their extracts possess antiviral properties and are studied with respect to coronavirus treatments. Chemical information, plant source, test system type with a mechanism of action for each secondary metabolite are also mentioned in this review paper. Conclusion: The present review has listed plants that have presented antiviral potential in the previous coronavirus pandemics and their secondary metabolites, which could be significant for the development of novel and a safer drug which could prevent and cure coronavirus infection worldwide.

The current 2019-nCoV outbreak is becoming extremely harmful and has affected the whole world. Its control is challenging because there is no effective vaccine or drug available for coronavirus disease. The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), previously named as 2019 novel coronavirus (2019-nCoV), primarily targets the human respiratory system to lung lesions and lethal pneumonia. Natural products have always shown a crucial role in the process of drug development against various diseases. They may serve as leads for further drug development to combat emergent mutants of the coronavirus. In this review, the current status of natural compounds and their derivatives acting against different species of CoV are discussed.

A recent outbreak of novel coronavirus (nCoV-19) has put an enormous burden on global public health. Millions of people were affected by this pandemic, and as of now, no effective antiviral drug has been found for the management of this situation. Cytokine storm, acute respiratory distress, hypoxia and multi-organ failure are hallmark clinical conditions of this disease. Trials for several investigational and repurposed drugs are being conducted, but none of them were found to be safe and effective. However, for the critically ill patient, plasma therapy, dexamethasone, and remdesivir are included in the treatment protocol. For a long time, various natural drugs have been used as antiviral agents in Indian and Chinese traditional medicines, which can be explored as a potential therapeutic option in such situation. It is, therefore, speculated that the proper screening and standardization of these medicines can be a breakthrough in the management and treatment of nCoV-19 infection. As natural products possess antioxidant, anti-inflammatory, anti-apoptotic, immunomodulatory properties and also specifically act on various viral enzymatic machinery and affect their replication process, thus they may be useful as alternatives in relieving symptoms and treatment of nCoV-19 infection. However, only on the basis of their traditional value, discrimination and off-label use of these natural drugs must be prevented, and robust preclinical and clinical data along with appropriate guidelines are needed for them to enter into clinical practice.

Background: The spread of COVID-19 has become a growing cause of mortalities over the globe since its major outbreak in December 2019. The scientific and medical communities are rallying to study different strains and probable mutations to develop more rapid and reliable molecular diagnostic tests and possible therapeutic approaches for SARS-CoV-2. Introduction: In the first section, following the introductory part, we shed light on structural and pathogenic features of SARS-CoV-2 and risk factors related to age, gender, neonatal and comorbidities. The next section summarizes the current diagnostic tests for COVID-19, such as nucleic acid and computed tomography (CT) techniques, with further emphasis on emerging diagnostic approaches for COVID-19. Methods: Further, we also review the ongoing therapeutic practices which can block virus-host interaction, cease viral proliferation or inhibit hyperbolic host immune response with subsections on drug therapy, cell therapy, immunotherapy and herbal medicines that are being used for the possible treatment of patients. Results and Conclusion: Among the different promising drugs, remdesivir, by inhibiting the RNA-dependent RNA-Polymerase activity, gives much better results, including declined viral load and quick lung tissue recovery. The long-lasting repercussions of COVID-19 have also been discussed at the end. In this review, we have also critically discussed the progress in several vaccines that are under development.

SARS-CoV-2, a positive single-stranded RNA enveloped coronavirus, currently poses a global health threat. Drugs with quinoline scaffolds have been studied to repurpose their useful broad-spectrum properties into treating various diseases, including viruses. Preliminary studies on the quinoline medications, chloroquine and hydroxychloroquine, against SARS-CoV-2, have shown to be a potential area of interest for drug development due to their ability to prevent viral entry, act as anti-inflammatory modulators, and inhibit key enzymes allowing reduced viral infectivity. In addition to Chloroquine and Hydroxychloroquine, we discussed analogs of the drugs to understand the quinoline scaffold’s potential antiviral mechanisms. The heterocyclic scaffold of quinoline can be modified in many ways, primarily through the modification of its substituents. We studied these different synthetic derivatives to understand properties that could enhance its antiviral specificity thoroughly. Chloroquine and its analogs can act on various stages of the viral life cycle, pre and post entry. In this study, we reviewed chloroquine and its synthetic and natural analogs for their antiviral properties in a variety of viruses. Furthermore, we reviewed the compound’s potential abilities to attenuate symptoms associated with viral infections. Natural compounds that share scaffolding to chloroquine can act as antivirals or attenuate symptoms through the stimulation of the host immune system or reduction of oxidative stress. Furthermore, we discuss perspectives of the drug’s repurposing due to its ability to inhibit the beta-hematin formation and to be a Zinc Ionophore.

Background: To date, more than thirty animals have been tested positive for SARS-CoV-2; all of them infected by humans with COVID-19. Some animal experiments suggested the possibility of animal to animal transmission of SARS-CoV-2 that was seen in some cases of infected animals. Animal to human transmission was considered unlikely until investigations revealed the possibility of mink to human transmission of SARS-CoV-2 in the Netherlands. 1 Objective: The current study aims at highlighting the predominance of SARS-CoV-2 infection in various animal species, reverse zoonotic transmission and proposing possible animal models that might aid in the study and development of a vaccine against Covid-19. Methods: The authors have gathered information on various animal species infected with SARS-CoV-2 and possible tests conducted via online news reports, websites and Scopus indexed journals. Results: The study of the susceptibility of SARS-CoV-2 to domestic animals concluded that pigs, chicken, and ducks were not vulnerable to Covid-19; dogs showed less susceptibility to SARS-CoV-2 and cats as well as ferrets were seen susceptible to Covid-19. SARS-CoV-2 has been seen crossing the species barrier, infecting humans from the wild with the yet unclear source, spreading from humans to humans quickly, humans to animals, animals to animals, and is likely to spread from animals to humans even though minimally. Animals appear somewhat resistant to SARS-CoV-2 transmission compared to humans who globally crossed eight million infection cases, and the infected animals mostly do not show many complications and recover quickly. Conclusion: Precautions are advised to prevent human to animal transmission of the virus, and in some areas, to avoid animal to human spread of the virus. Further monitoring is required to assess the SARS-CoV-2 infection in animals as COVID-19 is a rapidly evolving condition worldwide. Cats and ferrets have physiological resemblance and genome sequencing studies propose the possibility of these species to be used as animal models for investigating the SARS-CoV-2 infection and this might aid in further studies and vaccine development against Covid-19.

Background: The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin- converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). Methods: Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR), for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots. Results: These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site. Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor. At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2 but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus. These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues (Tyr343, and His235) of Endoribonuclease (NSP15) protein. Conclusion: The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of COVID-19 till some better option available.

: There is increasing evidence that lncRNA, a type of transcript that is over 200 nucleotides in length and may serve as oncogenes or suppressor genes, is implicated in the pathophysiology of human diseases. In particular, tumorigenesis and progress are closely correlated with its abnormal expression. In addition, it may become a promising target for many oncology biotherapies. Abnormal DLX6-AS1 expression affects different cellular processes such as proliferation, aggression and metastasis. This review aims to probe into the pathophysiological functions and molecular mechanisms of DLX6-AS1 in various cancers. Methods: By retrieving the literature, this review summarizes the biological function and mechanism of LncRNA DLX6-AS1 in tumor occurrence. Results: The lncRNA DLX6-AS1 is a new tumor-related RNA that has recently been found to be aberrantly expressed in diverse cancers, such as pancreatic cancer, osteosarcoma, non-small cell lung cancer, gastric carcinoma, glioma, hepatocellular cancer, colorectal carcinoma, renal carcinoma, esophageal squamous cell cancer, ovarian cancer, Ewing sarcoma, cervical cancer, breast cancer, thyroid cancer, neuroblastoma, pulmonary adenocarcinoma, nasopharyngeal carcinoma, squamous laryngeal cancer and bladder cancer, etc. Meanwhile, it is identified that DLX6-AS1 regulates the aggression, translocation and proliferation of diverse cancers. Conclusion: LncRNA DLX6-AS1 may be viable markers in tumors or a potential therapeutic target for multiple tumors.

Background: N⁶-methyladenosine (m⁶A) plays critical roles in a broad range of biological processes. Knowledge about the precise location of m⁶A site in the transcriptome is vital for deciphering its biological functions. Although experimental techniques have made substantial contributions to identify m⁶A, they are still labor intensive and time consuming. As complement to experimental methods, in the past few years, a series of computational approaches have been proposed to identify m⁶A sites. Methods: In order to facilitate researchers to select appropriate methods for identifying m⁶A sites, it is necessary to conduct a comprehensive review and comparison of existing methods. Results: Since research works on m⁶A in Saccharomyces cerevisiae are relatively clear, in this review, we summarized recent progress of computational prediction of m⁶A sites in S. cerevisiae and assessed the performance of existing computational methods. Finally, future directions of computationally identifying m⁶A sites are presented. Conclusion: Taken together, we anticipate that this review will serve as an important guide for computational analysis of m⁶A modifications.