Nanoformulation of Glycyrrhizic acid as a potent antiviral agent against Covid-19

In many previous studies, it has been found that liquorice plant (Glycyrrhiza glabra) extracts contain more than 300 natural compounds, most of which are triterpenoids and flavonoids, and had shown promising results in clinical studies for treating many microbial and viral infections. Triterpenoids like glycyrrhizic acid have shown anti-SARS-CoV activity in- vitro. Experimentally, certain glycyrrhizic acid derivatives have shown increased activity by many folds against SARS-associated viruses. These compounds can potentially inhibit the replication cycle of SARS-associated viruses by interfering with the viral gene expression or by inhibiting the spike protein expression, which in turn inhibits the adhesion and entry of the virus. Although the therapeutic has shown great antiviral activity in vitro, but in vivo its efficiency deteriorates till it reaches the liver for metabolism. In the current review, we analyze the unique replication strategy of SARS-CoV-2 and glycyrrhizic acid as a potential drug against SARS-CoV-2. We also discuss possible nano-formulations of glycyrrhizic acid for efficient drug delivery in humans, as a potent therapeutic strategy for COVID-19.

Antiviral Activities of High Energy E-Beam Induced Copper Nanoparticles against H1N1 Influenza Virus

The pandemic outbreak of COVID-19 in the year of 2020 that drastically changed everyone’s life has raised the urgent and intense need for the development of more efficacious antiviral material. This study was designed to develop copper nanoparticles (Cu NPs) as an antiviral agent and to validate the antiviral activities of developed copper NP. The Cu NPs were synthesized using a high energy electron beam, and the characteristic morphologies and antiviral activities of Cu NPs were evaluated. We found that Cu NPs are of spherical shape and uniformly distributed, with a diameter of around 100 nm, as opposed to the irregular shape of commercially available copper microparticles (Cu MPs). An X-ray diffraction analysis showed the presence of Cu and no copper oxide II and I in the Cu NPs. A virus inactivation assay revealed no visible viral DNA after 10- and 30-min treatment of H1N1 virus with the Cu NPs. The infectivity of the Cu NPs-treated H1N1 virus significantly decreased compared with that of the Cu MPs-treated H1N1 virus. The viability of A549 bronchial and Madin-Darby Canine Kidney (MDCK) cells infected with Cu NPs-treated H1N1 was significantly higher than those infected with Cu MPs-treated H1N1 virus. We also found cells infected with Cu NPs-treated H1N1 virus exhibited a markedly decreased presence of virus nucleoprotein (NuP), an influenza virus-specific structural protein, compared with cells infected with Cu MPs-treated H1N1 virus. Taken together, our study shows that Cu NPs are a more effective and efficacious antiviral agent compared with Cu MPs and offer promising opportunities for the prevention of devastatingly infectious diseases.

Unveiling of Pyrimidindinones as Potential Anti-Norovirus Agents—A Pharmacoinformatic-Based Approach

The RNA-dependent RNA polymerase (RdRp) receptor is an attractive target for treating human norovirus (HNV). A computer-aided approach like e-pharmacophore, molecular docking, and single point energy calculations were performed on the compounds retrieved from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database to identify the antiviral agent that could target the HNV RdRp receptor. Induced-fit docking (IFD) results showed that compounds ZINC1617939, ZINC1642549, ZINC6425208, ZINC5887658 and ZINC32068149 bind with the residues in the active site-B of HNV RdRp receptor via hydrogen bonds, salt bridge, and electrostatic interactions. During the molecular dynamic simulations, compounds ZINC6425208, ZINC5887658 and ZINC32068149 displayed an unbalanced backbone conformation with HNV RdRp protein, while ZINC1617939 and ZINC1642549 maintained stability with the protein backbone when interacting with the residues. Hence, the two new concluding compounds discovered by the computational approach can be used as a chemotype to design promising antiviral agents aimed at HNV RdRp.

Remdesivir for Covid-19 pneumonia in patients with severe chronic kidney disease: Case series and review of the literature

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.

Characteristics, Comorbidities, and Vaccination of COVID-19

COVID- 19 (Coronavirus disease 2019) is a quite contagious disease this is derived from Orthocoronavirinae family. SARS-CoV-2 viruses are single-stranded, plus-stranded RNA virus that infect numerous animal species, inclusive of humans, and cause respiration, neurological, and liver illnesses. SARS-CoV-2 is generally transferred through respiration droplets during close contact including speaking, coughing, sneezing, and shouting. Typical common symptoms of COVID-19 include respiratory symptoms like Fever and cough, diarrhea, nausea, vomiting, loss of appetite, and neurological manifestations. COVID-19 has currently been recognized using a viral nucleic acid RT-PCR test primarily based totally on affected person nasopharyngeal and throat swabs. The CT score could play a important function in the prognosis of COVID-19 infected patients if the RT-PCR test for swabs became negative at an early stage. COVID-19 patients with comorbidites like Diabetes Mellitus, Hypertension, Asthma, Deep Vein Thrombosis, Chronic Obstructive Pulmonary Disease (COPD), Cardio Vascular Disease, Obesity, Renal Disease, Liver Disease and other comorbidities can develope life-threatening situation. Remdesvir is the primary preference of medication, an antiviral agent that works via way of means of inhibiting viral replication in the body. There is a higher death rate in men while in comparison to women, hypothetically because of sex-based immunological or gendered differences. Vaccines are regarded as the maximum efficient way to halt the pandemic. Keywords: COVID-19, SARS-CoV-2, RT-PCR, comorbity, treatment, vaccine.

In Silico Study of Pubchem Compounds for Solanum torvum as Antiviral Agent against SARS-CoV-2

Background: The recent epidemic outbreak of a novel coronavirus called SARS-CoV-2 has caused suffering among many people in the form of respiratory tract infection. Currently, there are no targeted drugs, and effective treatment options remain limited. Objective: In order to rapidly discover new compounds for clinical purposes, in silico drug design and virtual drug screening have been initiated to identify new drug leads that target the main protease of the COVID-19 virus. Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus. Methods: The present study was done to investigate the PubChem compounds of an ayurvedic herb Solanum torvum as an effective antiviral agent against COVID-19. The PubChem compounds like Torvoside H, Torvoside A, Torvoside E, Torvoside F, Torvonin A, 2,3,4-trimethyltriacontane, Torvanol A Q27134802, 5-hexatriacontanone, Jurubine, Tritriacontan-3-one, Torvanol A, Chlorogenone Spirostane-3,6-dione of Solanum torvum were downloaded from NCBI PubChem database acting as ligands for protein ligand docking. The 3D structure of the viral MPro (PDB ID: 6yb7) was retrieved from the RCSB PDB database. The active sites and binding sites were analyzed, and Docking molecular simulations were realized among a total of 12 ligands against COVID-19. Results: The PubChem compounds from the fruits of Solanum torvum showed good docking score and protein-ligand interaction, indicating that the PubChem compounds can cure the COVID-19 disease and act as an effective antiviral agent. Conclusion: Most of the PubChem compounds in the fruits of Solanum torvum showed better paramagnetic parameters.

The Use of Convalescent Plasma (CP) Transfusion Therapy in Moderate to Severe COVID-19 Patients: a Single Center Experience in Indonesia

Background: Coronavirus disease 2019 (COVID-19) was declared as a world pandemic since early 2020. There was no specific antiviral agent that appeared to be active against the virus, and antiviral agent such as remdesivir, favipiravir were in limited supply. We evaluated the use of convalescent plasma (CP) administered as adjuctive treatment to standard of care in moderate to severe COVID-19 patients. Methods: We conducted a series of 9 moderate to severe patients of COVID-19 older than 18 years received CP transfusion from 9 recovered donors at a single institution (Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia) from January 2021 to June 2021. Results: Out of 9 patients (age range 30-81 years, 6 males and 3 female), and all patients received at least 1 or 2 unit of 200 mL of CP from 9 recovered donors. There were 4 patients (age range 30-71 years, 4 male) that were not treated with antiviral therapy. Of the 9 patients, 2 severe cases were died, while all of moderate cases survived and they were discharged from the hospital (length of stay: 8-22 days). Conclusion: Our experience showed that CP transfusion in moderate COVID-19 patients might provide clinical benefit and it was well-tolerated. However, further development clinical trials with better designs and greater power is needed to evaluate the efficacy and safety of this treatment.

Identification and Semisynthesis of (–)-Anisomelic Acid as an Oral Antiviral Agent against SARS-CoV-2 in Mice

(–)-Anisomelic acid (AA), isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-β-lactone motif. Cytopathic effect assays showed that the anti-SARS-CoV-2 effect of AA (IC50 = 4.3 μM) is comparable to that of remdesivir (IC50 = 2.1 μM), and more potent than that of molnupiravir (IC50 = 27.8 μM). Challenge studies in SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of AA and remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of AA from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing AA-based novel ligands for selectively targeting proteins involved in viral infection.

Exploration of Luteolin as Potential Anti-COVID19 agent: Molecular Docking, Molecular Dynamic Simulation, ADMET and DFT analysis

Background: Recently, coronavirus disease-2019 (COVID-19) has become a pandemic disease of the respiratory tract having mild to severe symptoms of pneumonia. No clinical antiviral agent is available so far, however, several repurposing drugs and vaccine are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools Method: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other chemical descriptors analysis Results: In the present study, Lut binds effectively in the binding pockets of spike glycoprotein (6VSB), ADP phosphatase of NSP3 (6W02), and RNA dependent RNA polymerase (7AAP) protein receptors with significant values of docking scores -7.00, -7.25, and -6.46 respectively as compared to reference drugs remdesivir and nafamostat. Conclusion:: Thus, Lut can act as therapeutic agent and is orally safe for human consumption as predicted by molecular modelling against SARS-CoV-2 in the treatment of COVID-19

Influence of Ribavirin on Mumps Virus Population Diversity

Frequent mumps outbreaks in vaccinated populations and the occurrence of neurological complications (e.g., aseptic meningitis or encephalitis) in patients with mumps indicate the need for the development of more efficient vaccines as well as specific antiviral therapies. RNA viruses are genetically highly heterogeneous populations that exist on the edge of an error threshold, such that additional increases in mutational burden can lead to extinction of the virus population. Deliberate modulation of their natural mutation rate is being exploited as an antiviral strategy and a possibility for rational vaccine design. The aim of this study was to examine the ability of ribavirin, a broad-spectrum antiviral agent, to introduce mutations in the mumps virus (MuV) genome and to investigate if resistance develops during long-term in vitro exposure to ribavirin. An increase in MuV population heterogeneity in the presence of ribavirin has been observed after one passage in cell culture, as well as a bias toward C-to-U and G-to-A transitions, which have previously been defined as ribavirin-related. At higher ribavirin concentration, MuV loses its infectivity during serial passaging and does not recover. At low ribavirin concentration, serial passaging leads to a more significant increase in population diversity and a stronger bias towards ribavirin-related transitions, independently of viral strain or cell culture. In these conditions, the virus retains its initial growth capacity, without development of resistance at a whole-virus population level.