Revolutionizing Playing with Skeleton Atoms: Molecular Editing Surgery in Medicinal Chemistry.

Finding the most perfect drug candidates in the fields of drug discovery and medicinal chemistry will remain the main interest of drug designers. This concern necessitates organic and medicinal chemists, in most examples, to precisely design and search for drug candidates that are very analogous to the present effective drugs with solving, mainly, their proven critical pharmacological and clinical issues through slightly changing one or two atoms of the principal functional skeletons of the molecules of these present therapeutics by atom swapping, removal, and/or addition procedures in organic chemical synthesis. This accurate modern chemicosimilarity tactic in drug discovery surely saves time while keeping us very close, or sometimes highly superior, to the parent pharmacophoric bioactivity (i.

Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies.

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential.

RNA: The most attractive target in recent viral diseases.

As an expert in the field of drug design and discovery, I tried, in this up-to-date perspective or commentary article, to recap and shed light on the previous and latest revolutionary strategies employed in medicinal and therapeutic chemistry to target the principal viral weapon used by virulent RNA viruses (e.g., the severe acute respiratory syndrome coronavirus 2 "SARS-CoV-2") to infect humans and spread infections, the genomic RNA strands.

Promising Experimental Anti-SARS-CoV-2 Agent "SLL-0197800": The Prospective Universal Inhibitory Properties against the Coming Versions of the Coronavirus.

Isoquinoline derivatives having some nucleosidic structural features are considered as candidate choices for effective remediation of the different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their following disease, the coronavirus disease 2019 (COVID-19). SLL-0197800 is a recently discovered isoquinoline compound with potential strong universal anticoronaviral activities against SARS-CoV-2 and its previous strains. SLL-0197800 nonspecifically hits the main protease (M) enzyme of the different coronaviruses.

Forodesine and Riboprine Exhibit Strong Anti-SARS-CoV-2 Repurposing Potential: and Studies.

Lately, nucleos(t)ide antivirals topped the scene as top options for the treatment of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Targeting the two broadly conserved SARS-CoV-2 enzymes, RNA-dependent RNA polymerase (RdRp) and 3'-to-5' exoribonuclease (ExoN), together using only one shot is a very successful new tactic to stop SARS-CoV-2 multiplication irrespective of the SARS-CoV-2 variant type. Herein, the current studies investigated most nucleoside analogue (NA) libraries, searching for the ideal drug candidates expectedly able to act through this double tactic.

The role of in inducing/aggravating IgE-mediated allergic airway disease: extensive computational studies for identification of allergenic proteins.

Respiratory allergies have become a major public health concern and affect one-third of the world's population. Several factors like environmental changes, industrialization, and immunologic interactions are reported to contribute to allergic respiratory diseases. Immunological reactions because of mosquito bite (allergic proteins) have been reported to have a high contribution to IgE-mediated allergic airway disease but they are largely ignored.

A peek behind the curtain in the diagnosis and management of COVID‑19‑Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration.

Dual computational and biological assessment of some promising nucleoside analogs against the COVID-19-Omicron variant.

Nucleoside analogs/derivatives (NAs/NDs) with potent antiviral activities are now deemed very convenient choices for the treatment of coronavirus disease 2019 (COVID-19) arisen by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. At the same time, the appearance of a new strain of SARS-CoV-2, the Omicron variant, necessitates multiplied efforts in fighting COVID-19. Counteracting the crucial SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3'-to-5' exoribonuclease (ExoN) jointly altogether using the same inhibitor is a quite successful new plan to demultiplicate SARS-CoV-2 particles and eliminate COVID-19 whatever the SARS-CoV-2 subtype is (due to the significant conservation nature of RdRps and ExoNs in the different SARS-CoV-2 strains).

Novel Investigational Anti-SARS-CoV-2 Agent Ensitrelvir "S-217622": A Very Promising Potential Universal Broad-Spectrum Antiviral at the Therapeutic Frontline of Coronavirus Species.

Lately, nitrogenous heterocyclic antivirals, such as nucleoside-like compounds, oxadiazoles, thiadiazoles, triazoles, quinolines, and isoquinolines, topped the therapeutic scene as promising agents of choice for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying ailment, the coronavirus disease 2019 (COVID-19). At the same time, the continuous emergence of new strains of SARS-CoV-2, like the Omicron variant and its multiple sublineages, resulted in a new defiance in the enduring COVID-19 battle. Ensitrelvir (S-217622) is a newly discovered orally active noncovalent nonpeptidic agent with potential strong broad-spectrum anticoronaviral activities, exhibiting promising nanomolar potencies against the different SARS-CoV-2 variants.

Strong Dual Antipolymerase/Antiexonuclease Actions of Some Aminothiadiazole Antioxidants: A Promising / Repurposing Research Study against the COVID-19 Omicron Virus (B.1.1.529.3 Lineage).

Currently, nitrogen-containing heterocyclic virucides take the lead as top options for treating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their escorting disease, the coronavirus disease 2019 (COVID-19). But unfortunately, the sudden emergence of a new strain of SARS-CoV-2, the Omicron variant and its lineages, complicated matters in the incessant COVID-19 battle. Goaling the two paramount coronaviral-2 multiplication enzymes RNA-dependent RNA polymerase (RdRp) and 3'-to-5' exoribonuclease (ExoN) at synchronous times using single ligand is a quite effective new binary avenue to restrain SARS-CoV-2 reproduction and cease COVID-19 progression irrespective of the SARS-CoV-2 strain type, as RdRps and ExoNs are vastly conserved in all SARS-CoV-2 strains.

A Series of Adenosine Analogs as the First Efficacious Anti-SARS-CoV-2 Drugs against the B.1.1.529.4 Lineage: A Preclinical Repurposing Research Study.

Given the rapid progression of the coronavirus disease 2019 (COVID-19) pandemic, an ultrafast response was urgently required to handle this major public crisis. To contain the pandemic, investments are required to develop diagnostic tests, prophylactic vaccines, and novel therapies. Lately, nucleoside analog (NA) antivirals topped the scene as top options for the treatment of COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.

Potent Dual Polymerase/Exonuclease Inhibitory Activities of Antioxidant Aminothiadiazoles Against the COVID-19 Omicron Virus: A Promising In Silico/In Vitro Repositioning Research Study.

Recently, natural and synthetic nitrogenous heterocyclic antivirals topped the scene as first choices for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying disease, the coronavirus disease 2019 (COVID-19). Meanwhile, the mysterious evolution of a new strain of SARS-CoV-2, the Omicron variant and its sublineages, caused a new defiance in the continual COVID-19 battle. Hitting the two principal coronaviral-2 multiplication enzymes RNA-dependent RNA polymerase (RdRp) and 3'-to-5' exoribonuclease (ExoN) synchronously using the same ligand is a highly effective novel dual pathway to hinder SARS-CoV-2 reproduction and stop COVID-19 progression irrespective of the SARS-CoV-2 variant type since RdRps and ExoNs are widely conserved among all SARS-CoV-2 strains.

Evaluation of a series of nucleoside analogs as effective anticoronaviral-2 drugs against the Omicron-B.1.1.529/BA.2 subvariant: A repurposing research study.

Mysterious evolution of a new strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the Omicron variant, led to a new challenge in the persistent coronavirus disease 2019 (COVID-19) battle. Objecting the conserved SARS-CoV-2 enzymes RNA-dependent RNA polymerase (RdRp) and 3'-to-5' exoribonuclease (ExoN) together using one ligand is a successful new tactic to stop SARS-CoV-2 multiplication and COVID-19 progression. The current comprehensive study investigated most nucleoside analogs (NAs) libraries, searching for the most ideal drug candidates expectedly able to act through this double tactic.

Efficacious Preclinical Repurposing of the Nucleoside Analogue Didanosine against COVID-19 Polymerase and Exonuclease.

Analogues and derivatives of natural nucleosides/nucleotides are considered among the most successful bioactive species of drug-like compounds in modern medicinal chemistry, as they are well recognized for their diverse and efficient pharmacological activities in humans, especially as antivirals and antitumors. Coronavirus disease 2019 (COVID-19) is still almost incurable, with its infectious viral microbe, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak devastation around the world. This global crisis pushed all involved scientists, including drug discoverers and clinical researchers, to try to find an effective and broad-spectrum anti-COVID-19 drug.

Retraction Note to: Discovery of ()--(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20): the first potent and specific anti-COVID-19 drug.

[This retracts the article DOI: 10.1007/s11696-021-01640-9.].

Potent Inhibitory Activities of the Adenosine Analogue Cordycepin on SARS-CoV-2 Replication.

Nucleoside analogues are among the most successful bioactive classes of druglike compounds in pharmaceutical chemistry as they are well-known for their numerous effective bioactivities in humans, especially as antiviral and anticancer agents. Coronavirus disease 2019 (COVID-19) is still untreatable, with its causing virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continuing to wreak havoc on the ground everywhere. This complicated international situation urged all concerned scientists, including medicinal chemists and drug discoverers, to search for a potent anti-COVID-19 drug.

Teriflunomide: A possible effective drug for the comprehensive treatment of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has undoubtedly become a global crisis. Consequently, discovery and identification of new or known potential drug candidates to solve the health problems caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become an urgent necessity. This current research study sheds light on the possible direct repurposing of the antirheumatic drug teriflunomide to act as an effective and potent anti-SARS-CoV-2 agent.

Discovery of Taroxaz-104: The first potent antidote of SARS-CoV-2 VOC-202012/01 strain.

Polyhydroxyphenols and nitrogenous heterocyclics are two of the most powerful active species of molecules in pharmaceutical chemistry, as each of them is renowned for its various bioactivities for humans. One of their outstanding actions is the antiviral activities, which clearly appear if the principal functional entities of both classes meet into one compound. The recent COVID-19 pandemic pushed us to computationally sift and assess our small library of synthetic 2-(3,4,5-trihydroxyphenyl)-1,3,4-oxadiazoles against the main coronaviral protein/enzymatic targets.

Cyanorona-20: The first potent anti-SARS-CoV-2 agent.

Explicit hindrance and blockade of the viral RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is considered one of the most promising and efficient approaches for developing highly potent remedies for COVID-19. However, almost all of the reported viral RdRp inhibitors (either repurposed or new antiviral drugs) lack specific selectivity against the novel coronaviral RdRp and still at a beginning phase of advancement. Herein, I discovered and introduce a new pyrazine derivative, (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 RdRp inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).

RETRACTED ARTICLE: Discovery of ()--(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20): the first potent and specific anti-COVID-19 drug.

Abstract: Specific inhibition of the viral RNA-dependent RNA polymerase (RdRp) of the newly-emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising strategy for developing highly potent medicines for coronavirus disease 2019 (COVID-19). However, almost all of the reported viral RdRp inhibitors (either repurposed drugs or new antiviral agents) lack selectivity against the SARS-CoV-2 RdRp. Herein, I discovered a new favipiravir derivative, ()--(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (cyanorona-20), as the first potent SARS-CoV-2 inhibitor with very high selectivity (209- and 45-fold more potent than favipiravir and remdesivir, respectively).

Potent toxic effects of Taroxaz-104 on the replication of SARS-CoV-2 particles.

Polyphenolics and 1,3,4-oxadiazoles are two of the most potent bioactive classes of compounds in medicinal chemistry, since both are known for their diverse pharmacological activities in humans. One of their prominent activities is the antimicrobial/antiviral activities, which are much apparent when the key functional structural moieties of both of them meet into the same compounds. The current COVID-19 pandemic motivated us to computationally screen and evaluate our library of previously-synthesized 2-(3,4,5-trihydroxyphenyl)-1,3,4-oxadiazoles against the major SARS-CoV-2 protein targets.

CoViTris2020 and ChloViD2020: a striking new hope in COVID-19 therapy.

Designing anticoronavirus disease 2019 (anti-COVID-19) agents is the primary concern of medicinal chemists/drug designers nowadays. Repurposing of known active compounds against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new effective and time-saving trend in anti-COVID-19 drug discovery. Thorough inhibition of the coronaviral-2 proteins (i.

Accurate conventional and microwave-assisted synthesis of galloyl hydrazide.

The usefulness of the structure of galloyl hydrazide (3,4,5-trihydroxybenzohydrazide, coded as in this article) as a privileged structural system in pharmaceutical organic and medicinal chemistry has prompted the advances of the further therapeutic potentials of this known antioxidant/antitumor compound and, in addition to that, it acts generally as a very important organic reaction intermediate for molecule planning (including synthesis of many important biologically active molecules), as it undergoes various types of chemical reactions. The data of the two synthetic methods (including the new green one), presented in this research article, provides sharp adequate chemical data about the challenging synthesis, separation (purification), and characterization of this compound. A new and very fast one-pot solventless greener microwave-assisted method of synthesis, in addition to the much slower old conventional one, is used in this present research; and followed by full precise purification and characterization (including chromatographic separation; physicochemical identification; IR, H-NMR, C-NMR, and mass spectroscopic analyses along with elemental analyses for structure elucidation) of .