A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Vol 20 (04) ◽  
pp. 417-432
Author(s):  
Mohd. Suhail
Keyword(s):  
Drug Design ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Chiral Drugs ◽  
Structure Based Drug Design ◽  
Drug Candidates ◽  
Main Protease ◽  
The World

It has been a great challenge for scientists to develop an anti-Covid drug/vaccine with fewer side effects, since the coronavirus pandemic began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle facing the world is not only the positive test of the patient recovered from coronavirus, but also the second wave of Covid-19. Hence, the world demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also ejects it or its material from the body completely. The current computational study not only utilizes a structure-based drug design approach to find possible drug candidates but also explains (i) why the prescription of chiral drugs was not satisfactory, (ii) what types of modification can make their prescription satisfactory, (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M[Formula: see text]) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the M[Formula: see text] of JC virus and SARS-CoV-2 were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The M[Formula: see text] of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The prescription of a combination of S-[Formula: see text]-hydroxychloroquine and [Formula: see text]-mefloquine is considered as a boon by the predicted study.

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2020 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Jc Virus ◽  
Computational Study ◽  
The Body ◽  
Biologically Active ◽  
Positive Test ◽  
Chiral Drugs ◽  
Racemic Form ◽  
Main Protease

<div>It has been a great challenge for the scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Besides, the mechanism of action and the reason of causing side effects, has also become a great challenge for the scientists in the case of chiral drugs. The main reason behind it, is the prescription of chiral drugs in the racemic form. Another hurdle in front of the world, is the positive test of the patient recovered from coronavirus. This</div><div>positive test of recovered person, shows the demand of such drugs whose mechanism is understandable, and which can block and eliminate SARS-CoV-2 or its material from the body completely, with fewer side effects. The presented computational study explains (i) the mechanism of action of drugs (chloroquine and hydroxychloroquine) that block SARS-CoV-2 (ii) the strength of mefloquine that may eliminate SARS-CoV-2. First, the binding affinities of main protease (Mpro) of JC virus for which mefloquine has already shown its strength to remove, were calculated. After that, same method was applied for SARS-CoV-2, and both the results were compared to know the strength of mefloquine against SARS-CoV-2. Till now, the experimental data found in the literature survey, was neither used in the interpretation nor evaluated computationally, in such a way, as I did for the first time to fight against the pandemic</div><div>situation. Hence, the current study includes the docking results and literature data for the prescription of a combination of only biologically active enantiomers to the patient fighting with coronavirus, with less side effect. Two enantiomers that could do it, are S-(+)hydroxychloroquine</div><div>and (+) mefloquine. Of course, one of these two drugs, will block the coronavirus, while another one will eliminate it.</div>

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2020 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Jc Virus ◽  
Computational Study ◽  
The Body ◽  
Biologically Active ◽  
Positive Test ◽  
Chiral Drugs ◽  
Racemic Form ◽  
Main Protease

<div>It has been a great challenge for the scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Besides, the mechanism of action and the reason of causing side effects, has also become a great challenge for the scientists in the case of chiral drugs. The main reason behind it, is the prescription of chiral drugs in the racemic form. Another hurdle in front of the world, is the positive test of the patient recovered from coronavirus. This</div><div>positive test of recovered person, shows the demand of such drugs whose mechanism is understandable, and which can block and eliminate SARS-CoV-2 or its material from the body completely, with fewer side effects. The presented computational study explains (i) the mechanism of action of drugs (chloroquine and hydroxychloroquine) that block SARS-CoV-2 (ii) the strength of mefloquine that may eliminate SARS-CoV-2. First, the binding affinities of main protease (Mpro) of JC virus for which mefloquine has already shown its strength to remove, were calculated. After that, same method was applied for SARS-CoV-2, and both the results were compared to know the strength of mefloquine against SARS-CoV-2. Till now, the experimental data found in the literature survey, was neither used in the interpretation nor evaluated computationally, in such a way, as I did for the first time to fight against the pandemic</div><div>situation. Hence, the current study includes the docking results and literature data for the prescription of a combination of only biologically active enantiomers to the patient fighting with coronavirus, with less side effect. Two enantiomers that could do it, are S-(+)hydroxychloroquine</div><div>and (+) mefloquine. Of course, one of these two drugs, will block the coronavirus, while another one will eliminate it.</div>

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2020 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Mechanism Of Action ◽  
Jc Virus ◽  
Computational Study ◽  
The Body ◽  
Biologically Active ◽  
Positive Test ◽  
Chiral Drugs ◽  
Racemic Form ◽  
Main Protease

<div>It has been a great challenge for the scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Besides, the mechanism of action and the reason of causing side effects, has also become a great challenge for the scientists in the case of chiral drugs. The main reason behind it, is the prescription of chiral drugs in the racemic form. Another hurdle in front of the world, is the positive test of the patient recovered from coronavirus. This</div><div>positive test of recovered person, shows the demand of such drugs whose mechanism is understandable, and which can block and eliminate SARS-CoV-2 or its material from the body completely, with fewer side effects. The presented computational study explains (i) the mechanism of action of drugs (chloroquine and hydroxychloroquine) that block SARS-CoV-2 (ii) the strength of mefloquine that may eliminate SARS-CoV-2. First, the binding affinities of main protease (Mpro) of JC virus for which mefloquine has already shown its strength to remove, were calculated. After that, same method was applied for SARS-CoV-2, and both the results were compared to know the strength of mefloquine against SARS-CoV-2. Till now, the experimental data found in the literature survey, was neither used in the interpretation nor evaluated computationally, in such a way, as I did for the first time to fight against the pandemic</div><div>situation. Hence, the current study includes the docking results and literature data for the prescription of a combination of only biologically active enantiomers to the patient fighting with coronavirus, with less side effect. Two enantiomers that could do it, are S-(+)hydroxychloroquine</div><div>and (+) mefloquine. Of course, one of these two drugs, will block the coronavirus, while another one will eliminate it.</div>

scholarly journals Toward the Identification of Potential α-Ketoamide Covalent Inhibitors for SARS-CoV-2 Main Protease: Fragment-Based Drug Design and MM-PBSA Calculations

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1004
Author(s):  
Mahmoud A. El Hassab ◽  
Mohamed Fares ◽  
Mohammed K. Abdel-Hamid Amin ◽  
Sara T. Al-Rashood ◽  
Amal Alharbi ◽  
...  
Keyword(s):  
Drug Design ◽  
Active Site ◽  
Binding Free Energy ◽  
Stable Complex ◽  
Active Site Residues ◽  
Structure Based Drug Design ◽  
Enzyme Active Site ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Covalent Docking

Since December 2019, the world has been facing the outbreak of the SARS-CoV-2 pandemic that has infected more than 149 million and killed 3.1 million people by 27 April 2021, according to WHO statistics. Safety measures and precautions taken by many countries seem insufficient, especially with no specific approved drugs against the virus. This has created an urgent need to fast track the development of new medication against the virus in order to alleviate the problem and meet public expectations. The SARS-CoV-2 3CL main protease (Mpro) is one of the most attractive targets in the virus life cycle, which is responsible for the processing of the viral polyprotein and is a key for the ribosomal translation of the SARS-CoV-2 genome. In this work, we targeted this enzyme through a structure-based drug design (SBDD) protocol, which aimed at the design of a new potential inhibitor for Mpro. The protocol involves three major steps: fragment-based drug design (FBDD), covalent docking and molecular dynamics (MD) simulation with the calculation of the designed molecule binding free energy at a high level of theory. The FBDD step identified five molecular fragments, which were linked via a suitable carbon linker, to construct our designed compound RMH148. The mode of binding and initial interactions between RMH148 and the enzyme active site was established in the second step of our protocol via covalent docking. The final step involved the use of MD simulations to test for the stability of the docked RMH148 into the Mpro active site and included precise calculations for potential interactions with active site residues and binding free energies. The results introduced RMH148 as a potential inhibitor for the SARS-CoV-2 Mpro enzyme, which was able to achieve various interactions with the enzyme and forms a highly stable complex at the active site even better than the co-crystalized reference.

scholarly journals Making the invisible enemy visible

2020 ◽  
Author(s):  
Tristan Croll ◽  
Kay Diederichs ◽  
Florens Fischer ◽  
Cameron Fyfe ◽  
Yunyun Gao ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Design ◽  
Structure Determination ◽  
Task Force ◽  
Protein Structures ◽  
Structural Models ◽  
Viral Proteins ◽  
Human Cells ◽  
Structure Based Drug Design ◽  
The Eu

AbstractDuring the COVID-19 pandemic, structural biologists rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 204 previously solved structures from SARS-CoV-1, 548 structures covering 16 of the SARS-CoV-2 viral proteins have been released in a span of only 6 months. These structural models serve as the basis for research to understand how the virus hijacks human cells, for structure-based drug design, and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and may be even more common among these structures, which were solved quickly and under immense pressure.The Coronavirus Structural Task Force has responded to this challenge by rapidly categorizing, evaluating and reviewing all of these experimental protein structures in order to help downstream users and original authors. In addition, the Task Force provided improved models for key structures online, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge and others.

Rational Drug Design

2014 ◽  
Vol 4 (1) ◽  
pp. 59-85 ◽  
Author(s):  
Khaled H. Barakat ◽  
Michael Houghton ◽  
D. Lorne Tyrrel ◽  
Jack A. Tuszynski
Keyword(s):  
Drug Design ◽  
Rational Drug Design ◽  
Dimensional Structure ◽  
Computational Tools ◽  
Structure Based Drug Design ◽  
Practical Applications ◽  
3 Dimensional ◽  
Drug Candidates ◽  
The Past ◽  
Rational Drug

For the past three decades rationale drug design (RDD) has been developing as an innovative, rapid and successful way to discover new drug candidates. Many strategies have been followed and several targets with diverse structures and different biological roles have been investigated. Despite the variety of computational tools available, one can broadly divide them into two major classes that can be adopted either separately or in combination. The first class involves structure-based drug design, when the target's 3-dimensional structure is available or it can be computationally generated using homology modeling. On the other hand, when only a set of active molecules is available, and the structure of the target is unknown, ligand-based drug design tools are usually used. This review describes some recent advances in rational drug design, summarizes a number of their practical applications, and discusses both the advantages and shortcomings of the various techniques used.

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