acyclovir and Coronavirus-Infections

We present a challenging case of a young patient who presented with focal neurological signs following a course of OC-43 coronavirus-related pneumonia almost 8 months before the COVID-19 outbreak.

Topics: Acyclovir; Antiviral Agents; Aspirin; Coronavirus Infections; Coronavirus OC43, Human; COVID-19; Humans; Ischemic Stroke; Magnetic Resonance Imaging; Male; Nasopharynx; Platelet Aggregation Inhibitors; Pneumonia, Viral; SARS-CoV-2; Treatment Outcome; Young Adult

Recently, a pathogen has been identified as a novel coronavirus (SARS-CoV-2) and found to trigger novel pneumonia (COVID-19) in human beings and some other mammals. The uncontrolled release of cytokines is seen from the primary stages of symptoms to last acute respiratory distress syndrome (ARDS). Thus, it is necessary to find out safe and effective drugs against this deadly coronavirus as soon as possible. Here, we downloaded the three-dimensional model of NSP10/NSP16 methyltransferase (PDB-ID: 6w6l) and main protease (PDB-ID: 6lu7) of COVID-19. Using these molecular models, we performed virtual screening with our anti-viral, inti-infectious, and anti-protease compounds, which are attractive therapeutics to prevent infection of the COVID-19. We found that top screened compound binds with protein molecules with good dock score with the help of hydrophobic interactions and hydrogen bonding. We observed that protease complexed with Cyclocytidine hydrochloride (anti-viral and anti-cancer), Trifluridine (anti-viral), Adonitol, and Meropenem (anti-bacterial), and Penciclovir (anti-viral) bound with a good docking score ranging from -6.8 to -5.1 (Kcal/mol). Further, NSP10/NSP16 methyltransferase complexed with Telbivudine, Oxytetracycline dihydrate (anti-viral), Methylgallate (anti-malarial), 2-deoxyglucose and Daphnetin (anti-cancer) from the docking score of -7.0 to -5.7 (Kcal/mol). In conclusion, the selected compounds may be used as a novel therapeutic agent to combat this deadly pandemic disease, SARS-CoV-2 infection, but needs further experimental research.HighlightsNSP10/NSP16 methyltransferase and main protease complex of SARS CoV-2 bind with selected drugs.NSP10/NSP16 methyltransferase and protease interacted with drugs by hydrophobic interactions.Compounds show good DG binging free energy with protein complexes.Ligands were found to follow the Lipinski rule of five.

Topics: Acyclovir; Ancitabine; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Evaluation, Preclinical; Guanine; Humans; Meropenem; Methyltransferases; Models, Molecular; Molecular Docking Simulation; Pandemics; Pneumonia, Viral; Protein Conformation; Ribitol; SARS-CoV-2; Trifluridine; User-Computer Interface; Viral Nonstructural Proteins; Viral Regulatory and Accessory Proteins

Topics: Acyclovir; Aged; Analgesics; Betacoronavirus; Coronavirus Infections; COVID-19; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Lymphocyte Count; Male; Pandemics; Pneumonia, Viral; SARS-CoV-2

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

Topics: Acyclovir; Antiviral Agents; Betacoronavirus; Brain; Coronavirus Infections; COVID-19; Female; Glial Fibrillary Acidic Protein; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Interleukin-6; Leukoencephalitis, Acute Hemorrhagic; Magnetic Resonance Imaging; Middle Aged; Neurofilament Proteins; Pandemics; Plasma Exchange; Pneumonia, Viral; Real-Time Polymerase Chain Reaction; RNA, Viral; SARS-CoV-2; tau Proteins; Tomography, X-Ray Computed; Viral Tropism

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug's safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.

Topics: Acyclovir; Antiviral Agents; Betacoronavirus; Biological Availability; Butyrates; Chemistry, Pharmaceutical; Chrysenes; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Drug Repositioning; Humans; Ionic Liquids; Pandemics; Pentacyclic Triterpenes; Pneumonia, Viral; SARS-CoV-2; Solubility

Topics: Acyclovir; Administration, Cutaneous; Administration, Oral; Adult; Antiviral Agents; Betacoronavirus; Child; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Female; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male; Ophthalmic Solutions; Pandemics; Pneumonia, Viral; Prednisolone; SARS-CoV-2; Treatment Outcome; Virus Activation

A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC50 >3× EC50) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC50 <10 μM and a CC50 >100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.

Topics: Acyclovir; Animals; Antiviral Agents; Chlorocebus aethiops; Coronavirus; Coronavirus Infections; Coronavirus NL63, Human; Drug Design; Humans; Middle East Respiratory Syndrome Coronavirus; Nucleosides; Severe acute respiratory syndrome-related coronavirus; Vero Cells; Virus Replication