The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.
Quercetin is a phenolic flavonol compound with established antioxidant, anti-inflammatory, and immuno-stimulant properties. Recent studies demonstrate the potential of quercetin against COVID-19. This article highlighted the prophylactic/therapeutic potential of quercetin against COVID-19 in view of its clinical studies, inventions, and patents. The literature for the subject matter was collected utilizing different databases, including PubMed, Sci-Finder, Espacenet, Patentscope, and USPTO. Clinical studies expose the potential of quercetin monotherapy, and also its combination therapy with other compounds, including zinc, vitamin C, curcumin, vitamin D3, masitinib, hydroxychloroquine, azithromycin, and ivermectin. The patent literature also examines claims that quercetin containing nutraceuticals, pharmaceuticals, and dietary supplements, alone or in combination with other drugs/compounds, including favipiravir, remdesivir, molnupiravir, navitoclax, dasatinib, disulfiram, rucaparib, tamarixin, iota-carrageenan, and various herbal extracts (aloe, poria, rosemary, and sphagnum) has potential for use against COVID-19. The literature reveals that quercetin exhibits anti-COVID-19 activity because of its inhibitory effect on the expression of the human ACE2 receptors and the enzymes of SARS-CoV-2 (MPro, PLPro, and RdRp). The USFDA designated quercetin as a “Generally Recognized as Safe” substance for use in the food and beverage industries. It is also an inexpensive and readily available compound. These facts increase the possibility and foreseeability of making novel and economical drug combinations containing quercetin to prevent/treat COVID-19. Quercetin is an acidic compound and shows metabolic interaction with some antivirals, antibiotics, and anti-inflammatory agents. Therefore, the physicochemical and metabolic drug interactions between quercetin and the combined drugs/compounds must be better understood before developing new compositions.
The development of remdesivir has been a breakthrough for COVID-19 treatment. It has been approved in about 50 countries, including Saudi Arabia, since 2020. The generic structure of remdesivir was first disclosed in 2009. This patent review summarizes the remdesivir based inventions to treat/prevent COVID-19 and other disorders from 2009 to May 16, 2021, emphasizing the patents related to medical and pharmaceutical sciences. The primary patents/patent applications of remdesivir are related to its compositions, new combinations with other therapeutic agents, delivery systems, and new indications. The inventive combinations have displayed synergistic effects against COVID-19, whereas the delivery systems/compositions have improved patient compliance. The inventions related to new indications of remdesivir to treat Ebola, hepatitis, idiopathic pulmonary fibrosis, diabetic nephropathy, and cardiovascular complications enhance its therapeutic area. Many new innovative combinations and delivery systems of remdesivir are anticipated to provide better treatment for COVID-19.
Densities, ultrasonic speeds and viscosities have been measured for benzyl alcohol, ethanol, propan-1-ol, octan-1-ol and for their binary mixtures with benzyl alcohol as common component at 303 K. From the experimental data, isentropic compressibility, relative association, acoustic impedance, molar sound velocity, excess volume, excess isentropic compressibility, deviations of viscosity and ultrasonic speed from linear dependence on composition, excess acoustic impedance and molecular association for all the three binary mixtures were obtained. These parameters have been interpreted in terms of intermolecular interactions. The experimental viscosity data of the three binary mixtures were used to test the validity of the empirical relations of Grunberg-Nissan, Tamura-Kurata, Hind-Mclaughlin, Katti-Chaudhary and Heric. The experimental values of ultrasonic speeds have been compared with those predicted on the basis of the Nomoto empirical relation, collision factor theory, free length theory and van Dael and Vangeel ideal mixing relation. The relative merits of these theories and relations are discussed.
The densities, r, and ultrasonic speeds, u, have been measured in the binary liquid mixtures of acetonitrile (ACN) with 1-hexanol, 1-octanol and 1-decanol, and in the pure components, as a function of composition at 25, 30, 35, 40 and 45°C. The deviations in isentropic compressibility, Dks, excess molar volume, V E , deviations in ultrasonic speed, Du, apparent molar compressibility, K f,2, apparent molar volume, Vf,2, partial molar compressibility,`K°f,2, and partial molar volume,`V°2, of 1-alkanols in ACN have been calculated from the experimental data of densities and ultrasonic speeds. The variations of these parameters with composition of the mixtures indicate that the structure-breaking effect dominates over that of the hydrogen-bonding effect between unlike molecules, suggesting that ACN-alkanol interaction is weaker than ACN-ACN and alkanolalkanol interactions, and that the interaction (ACN-alkanol) follows the order: 1-hexanol > 1-octanol > 1decanol. The excess molar volume data have been analysed by using Flory and Prigogine-Flory-Patterson theories. Further, the ultrasonic speeds in these mixtures were theoretically calculated with the help of several theories and empirical relations using the pure component data. The validity and relative merits of these theories and relations have been discussed.
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