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Journal of Receptor and Signal... Dec 2020Recently, 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...
Virtual screening, ADME/T, and binding free energy analysis of anti-viral, anti-protease, and anti-infectious compounds against NSP10/NSP16 methyltransferase and main protease of SARS CoV-2.
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; COVID-19; Coronavirus Infections; 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
PubMed: 32476594
DOI: 10.1080/10799893.2020.1772298 -
PeerJ 2022Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on...
BACKGROUND
Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity.
MATERIALS AND METHODS
Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot.
RESULTS
Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity.
CONCLUSION
Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of "old" drugs for "new" applications.
Topics: Ancitabine; DNA, Circular; DNA, Viral; DNA-Directed DNA Polymerase; Hepatitis B virus; Virus Replication
PubMed: 35846878
DOI: 10.7717/peerj.13719 -
The Tohoku Journal of Experimental... Jan 1978Since cyclocytidine (2,2'-anhydro-1-beta-arabinofuranosylcytosine hydrochloride) was introduced as an antineoplastic agent for the treatment of lymphatic leukemia, sinus...
Since cyclocytidine (2,2'-anhydro-1-beta-arabinofuranosylcytosine hydrochloride) was introduced as an antineoplastic agent for the treatment of lymphatic leukemia, sinus acceleration and an increase in systemic blood pressure has been reported as its systemic effects in the clinical cases. These cardiovascular effects of cyclocytidine were observed also in anesthetized dogs, but not in reserpine-pretreated animals. Increases in heart rate and in systemic blood pressure were prevented by propranolol and phentolamine, respectively. The mechanism of these sympathomimetic effects was further analysed in the excised, blood-perfused canine sinoatrial node and papillary muscle preparations with a support dog. Positive chronotropic and inotropic responses to cyclocytidine were abolished by desipramine, propanolol, and pretreatment with reserpine but not by tetrodotoxin and hexamethonium. The tyramine-like actions of cyclocytidine at adrenergic neuronal terminals were discussed in conjunction with the uptake mechanism of the drug into the tumor cells.
Topics: Ancitabine; Animals; Blood Pressure; Cytarabine; Dogs; Female; Heart Rate; In Vitro Techniques; Male; Papillary Muscles; Sinoatrial Node; Sympathomimetics; Tyramine
PubMed: 76345
DOI: 10.1620/tjem.124.83 -
Acta Haematologica 1992
Topics: Acute Disease; Adult; Ancitabine; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Humans; Male; Parotitis; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 1384258
DOI: 10.1159/000204597 -
Antimicrobial Agents and Chemotherapy Feb 1986The effects of 2,2'-O-cyclocytidine (CC) and acyclovir (ACV) on latent herpes simplex virus (HSV) in trigeminal ganglia were studied in an in vitro model using...
The effects of 2,2'-O-cyclocytidine (CC) and acyclovir (ACV) on latent herpes simplex virus (HSV) in trigeminal ganglia were studied in an in vitro model using reactivation of HSV type 1 (HSV-1) as a model. It was shown that both CC (10 micrograms/ml) and ACV (2.5 micrograms/ml) significantly inhibited the reactivation of the latent HSV-1 in infected ganglia. The effect of CC (25 micrograms/ml), which was as good as that of ACV (10 micrograms/ml), did not last as long as that of ACV after removal of the drugs. The latent state of HSV-1 in vitro was dependent on the continuous presence of either drug. Even though the latent HSV-1 could not be eliminated completely from the trigeminal ganglia by discontinuous administration of either drug, its titers were markedly reduced. The combination of CC and ACV had a synergistic effect on preventing the reactivation of the latent HSV-1 in vitro.
Topics: Acyclovir; Ancitabine; Animals; Culture Techniques; Cytarabine; Drug Therapy, Combination; Herpes Simplex; Mice; Mice, Inbred Strains; Simplexvirus; Time Factors; Trigeminal Ganglion; Trigeminal Nerve; Virus Replication
PubMed: 2424367
DOI: 10.1128/AAC.29.2.278 -
Antimicrobial Agents and Chemotherapy Feb 1977Antiviral activities of acyl derivatives (3'-O-octanoyl and 3'-O-decanoyl) of 2,2'-anhydro-1-beta-d-arabinofuranosylcytosine (cyclo-C) and...
Antiviral activities of acyl derivatives (3'-O-octanoyl and 3'-O-decanoyl) of 2,2'-anhydro-1-beta-d-arabinofuranosylcytosine (cyclo-C) and 1-beta-d-arabinofuranosylcytosine (Ara-C) were compared with other antiviral nucleosides, and some biological characteristics of the antiviral activity were investigated. Among those synthesized acyl derivatives, 3'-O-decanoyl ara-C was the most active against deoxyribonucleic acid viruses, with an activity comparable to that of Ara-C. Acyl derivatives of cyclo-C were somewhat less active than their Ara-C counterparts. In the value of therapeutic index, 1-beta-d-arabinofuranosyladenine was superior to the others, followed by 5-iodo-2'-deoxyuridine. In comparing the sensitivity of two serotypes of herpes simplex virus it was found that Ara-C and its ester, as well as its cyclo-C counterpart, were more active against the type 2 than the type 1 strain. The activity of 3'-O-decanoyl Ara-C, like that of its parent, was diminished by treatment with cytidine deaminase from mouse kidney, but 3'-O-decanoyl cyclo-C was resistant to this treatment. In comparative studies of 3'- and 5'-O-acyl Ara-C's, antivaccinia virus activity of 3'-O-palmitoyl Ara-C was significantly superior to its 5'-counterpart. The inhibitory activity of 5'-O-decanoyl Ara-C was markedly reduced by the presence of a threefold molar excess of eserine sulfate, a choline esterase inhibitor, whereas the 3'-acyl Ara-C was not affected by the inhibitor in any combination. This result indicates that enzymatic hydrolysis of the 3'-ester to Ara-C, which is inhibited by eserine sulfate, did not occur in this cell culture.
Topics: Acylation; Ancitabine; Animals; Antineoplastic Agents; Antiviral Agents; Cells, Cultured; Cytarabine; Depression, Chemical; Drug Resistance, Microbial; Haplorhini; Humans; Physostigmine; Rabbits; Structure-Activity Relationship; Viruses
PubMed: 66909
DOI: 10.1128/AAC.11.2.191 -
Cancer Treatment Reports Aug 1977Determination of the site of excessive hormone production in Cushing syndrome is possible with biochemical tests in 80% of cases. High-resolution CT of both the...
Determination of the site of excessive hormone production in Cushing syndrome is possible with biochemical tests in 80% of cases. High-resolution CT of both the pituitary and adrenal glands was used to evaluate eight patients with surgically verified ACTH-secreting pituitary microadenomas and one patient with ectopic Cushing syndrome. Three ACTH-secreting microadenomas were demonstrated by CT. Adrenal CT was normal in six of the eight patients with pituitary tumors. The patient with ectopic ACTH production had mild unilateral adrenal gland enlargement and a normal pituitary CT scan. Normal adrenal or pituitary CT scans do not exclude Cushing syndrome.
Topics: Administration, Oral; Ancitabine; Animals; Biotransformation; Cytarabine; Dogs; Drug Stability; Female; Haplorhini; Injections, Intravenous; Intestinal Absorption; Macaca mulatta; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Rats; Species Specificity; Time Factors
PubMed: 70271
DOI: No ID Found -
Zhongguo Yao Li Xue Bao = Acta... Jul 1988
Topics: Acyclovir; Ancitabine; Animals; Cytarabine; Drug Therapy, Combination; Keratitis, Dendritic; Rabbits; Simplexvirus
PubMed: 2461639
DOI: No ID Found