Radiation exposure in planned scenario necessarily requires radioprotector for protection against... more Radiation exposure in planned scenario necessarily requires radioprotector for protection against radiation injuries in tissues and organs. A large number of potential radioprotectors have been investigated but no approved radioprotector is available. Hence, in quest for radioprotector, repurposing of clinical drug is an approach which aims at finding the radioprotective potential of known drugs so that in case of untoward accident the knowledge could be translated to drug usage. In this study, we have investigated the radical scavenging properties of tetracycline pertaining to radioprotection. Our study suggests that tetracycline hydrochloride efficiently scavenges free radicals in ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. Hydroxyl radical scavenging assay has demonstrated its ability to scavenge gamma radiation induced free radicals by lowering the formation of malondialdehyde. Radiation causes damage to macromolecules and hence the protection offered by tetracycline hydrochloride to DNA and protein shows its radioprotective potential. Plasmid DNA relaxation study with pBR322 has shown that tetracycline hydrochloride confers dose modification factor (DMF) of 2 and 4 at 100 μM and 250 μM concentration respectively. Tetracycline hydrochloride has also protected bovine serum albumin (BSA) from radiation induced degradation. The ex vivo studies for lipid peroxidation and mitochondrial membrane potential further substantiate our findings. The whole body animal survival study has shown the drug to offer 20% protection at a lethal radiation dose of 9 Gy. This study demonstrates the radioprotective potential of the drug by providing some insight into ex vivo and in vivo efficacy.
Current Developments in the Detection and Control of Multi Drug Resistance
The phenomenon of drug resistance is a widely acknowledged problem in clinics. Drug resistance no... more The phenomenon of drug resistance is a widely acknowledged problem in clinics. Drug resistance not only increases the treatment time, but also paves the way for testing the maximum limit of dose tolerance of antibiotics in the patient. There is no escaping of the fact that drug tolerance may remain a perpetual problem and bacteria will keep on evolving as a part of the natural selection process. Therefore, novel drugs targeting the novel mechanism of action could be a proposed solution for this problem. The mechanism of action includes efflux pump, alteration/modification of drug target, enzyme inactivation and prevention of drug penetration. The other thing is to avoid the unnecessary usage of antibiotics so that the bacteria living inside the body do not develop resistance. The places where antibiotics can be bought for human or animal use without a prescription, the emergence and spread of resistance are made worse. Similarly, in countries without standard treatment guidelines, a...
Journal of Biomolecular Structure and Dynamics, 2021
Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human co... more Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
Journal of Biomolecular Structure and Dynamics, 2021
Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human co... more Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
Radiation exposure in planned scenario necessarily requires radioprotector for protection against... more Radiation exposure in planned scenario necessarily requires radioprotector for protection against radiation injuries in tissues and organs. A large number of potential radioprotectors have been investigated but no approved radioprotector is available. Hence, in quest for radioprotector, repurposing of clinical drug is an approach which aims at finding the radioprotective potential of known drugs so that in case of untoward accident the knowledge could be translated to drug usage. In this study, we have investigated the radical scavenging properties of tetracycline pertaining to radioprotection. Our study suggests that tetracycline hydrochloride efficiently scavenges free radicals in ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. Hydroxyl radical scavenging assay has demonstrated its ability to scavenge gamma radiation induced free radicals by lowering the formation of malondialdehyde. Radiation causes damage to macromolecules and hence the protection offered by tetracycline hydrochloride to DNA and protein shows its radioprotective potential. Plasmid DNA relaxation study with pBR322 has shown that tetracycline hydrochloride confers dose modification factor (DMF) of 2 and 4 at 100 μM and 250 μM concentration respectively. Tetracycline hydrochloride has also protected bovine serum albumin (BSA) from radiation induced degradation. The ex vivo studies for lipid peroxidation and mitochondrial membrane potential further substantiate our findings. The whole body animal survival study has shown the drug to offer 20% protection at a lethal radiation dose of 9 Gy. This study demonstrates the radioprotective potential of the drug by providing some insight into ex vivo and in vivo efficacy.
Radiation exposure in planned scenario necessarily requires radioprotector for protection against... more Radiation exposure in planned scenario necessarily requires radioprotector for protection against radiation injuries in tissues and organs. A large number of potential radioprotectors have been investigated but no approved radioprotector is available. Hence, in quest for radioprotector, repurposing of clinical drug is an approach which aims at finding the radioprotective potential of known drugs so that in case of untoward accident the knowledge could be translated to drug usage. In this study, we have investigated the radical scavenging properties of tetracycline pertaining to radioprotection. Our study suggests that tetracycline hydrochloride efficiently scavenges free radicals in ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. Hydroxyl radical scavenging assay has demonstrated its ability to scavenge gamma radiation induced free radicals by lowering the formation of malondialdehyde. Radiation causes damage to macromolecules and hence the protection offered by tetracycline hydrochloride to DNA and protein shows its radioprotective potential. Plasmid DNA relaxation study with pBR322 has shown that tetracycline hydrochloride confers dose modification factor (DMF) of 2 and 4 at 100 μM and 250 μM concentration respectively. Tetracycline hydrochloride has also protected bovine serum albumin (BSA) from radiation induced degradation. The ex vivo studies for lipid peroxidation and mitochondrial membrane potential further substantiate our findings. The whole body animal survival study has shown the drug to offer 20% protection at a lethal radiation dose of 9 Gy. This study demonstrates the radioprotective potential of the drug by providing some insight into ex vivo and in vivo efficacy.
Current Developments in the Detection and Control of Multi Drug Resistance
The phenomenon of drug resistance is a widely acknowledged problem in clinics. Drug resistance no... more The phenomenon of drug resistance is a widely acknowledged problem in clinics. Drug resistance not only increases the treatment time, but also paves the way for testing the maximum limit of dose tolerance of antibiotics in the patient. There is no escaping of the fact that drug tolerance may remain a perpetual problem and bacteria will keep on evolving as a part of the natural selection process. Therefore, novel drugs targeting the novel mechanism of action could be a proposed solution for this problem. The mechanism of action includes efflux pump, alteration/modification of drug target, enzyme inactivation and prevention of drug penetration. The other thing is to avoid the unnecessary usage of antibiotics so that the bacteria living inside the body do not develop resistance. The places where antibiotics can be bought for human or animal use without a prescription, the emergence and spread of resistance are made worse. Similarly, in countries without standard treatment guidelines, a...
Journal of Biomolecular Structure and Dynamics, 2021
Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human co... more Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
Journal of Biomolecular Structure and Dynamics, 2021
Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human co... more Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.
Radiation exposure in planned scenario necessarily requires radioprotector for protection against... more Radiation exposure in planned scenario necessarily requires radioprotector for protection against radiation injuries in tissues and organs. A large number of potential radioprotectors have been investigated but no approved radioprotector is available. Hence, in quest for radioprotector, repurposing of clinical drug is an approach which aims at finding the radioprotective potential of known drugs so that in case of untoward accident the knowledge could be translated to drug usage. In this study, we have investigated the radical scavenging properties of tetracycline pertaining to radioprotection. Our study suggests that tetracycline hydrochloride efficiently scavenges free radicals in ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays. Hydroxyl radical scavenging assay has demonstrated its ability to scavenge gamma radiation induced free radicals by lowering the formation of malondialdehyde. Radiation causes damage to macromolecules and hence the protection offered by tetracycline hydrochloride to DNA and protein shows its radioprotective potential. Plasmid DNA relaxation study with pBR322 has shown that tetracycline hydrochloride confers dose modification factor (DMF) of 2 and 4 at 100 μM and 250 μM concentration respectively. Tetracycline hydrochloride has also protected bovine serum albumin (BSA) from radiation induced degradation. The ex vivo studies for lipid peroxidation and mitochondrial membrane potential further substantiate our findings. The whole body animal survival study has shown the drug to offer 20% protection at a lethal radiation dose of 9 Gy. This study demonstrates the radioprotective potential of the drug by providing some insight into ex vivo and in vivo efficacy.
Uploads
Papers by Amit Alok