Recent Patents on Anti-Infective Drug Discovery - Volume 15, Issue 2, 2020

Coronavirus disease is a potentially deadly disease and of significant apprehension for global communal health because of its lethality. Vaccines and antiviral medications are still under trial to prevent or treat human coronavirus (HCoV) till date. The virus HCoV originated in 2003, SARS-CoV, which causes respiratory syndrome having distinctive pathogenesis and infections of the respiratory tract. A mechanism was projected for the evolution of SARS virus, and a handy association with bats was found. When this virus reaches the respective host system, the infection starts with spike protein binding to its complementary receptor of the host cell. The coronavirus spike protein’s association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. Recent studies show that SARS Coronavirus 2 or COVID-19 requires protease to get into cells, offering a new therapeutic target. Distinctive attention and exertions should be given to defending or reducing transmission in vulnerable populaces, including those directly associated with caregiving and treatment and also aged one. Researchers are planning to develop a vaccine for COVID-19, and in this approach are also considered developing a vaccine that sensitizes our immune system preventing from this pandemic. The present review focuses on the role of S-spike protein in COVID-19, which helps the virus intruding the enzyme ACE2 (Angiotensin-Converting Enzyme 2). Passive antibody therapy is an additional alternative to use blood donors from hale and hearty people who have already recovered from COVID-19 and therapeutic advancement in handling the COVID-19 pandemic.

To date, severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has infected millions of individuals worldwide. This virus causes coronavirus disease 2019 (COVID-19) and has led to numerous deaths worldwide. A large percentage of infected patients present asymptomatically, augmenting the spread of the virus. Symptomatic COVID-19 commonly causes mild to severe respiratory disease and fever, but some individuals experience serious complications resulting in death. Immune compromised, high risk, and elderly individuals are at an increased risk of more severe consequences of the illness such as respiratory failure, organ dysfunction, and shock. Cytokine storm (also known as cytokine release syndrome (CRS)), a systemic inflammatory response that can be triggered by an infection, has been associated with the symptom progression of COVID-19. This review evaluates several published studies that have implemented tocilizumab (TCZ), an IL-6 receptor antibody (US20120253016A1), in COVID-19 treatment. Outcomes and biomarkers of patients treated with TCZ are compared to patients treated with standard of care regimens. Interleukin-6 (IL-6), a prominent inflammatory cytokine involved in CRS in various inflammatory conditions, may have a vital role in the underlying mechanism involved in debilitating SARS-CoV-2 infections and could serve as a viable treatment target. Studies suggest that TCZ may aid in the recovery of patients with COVID-19 and reduce mortality.

Background: On 11th March 2020, WHO announced novel coronavirus infectious (COVID-19) as a pandemic. New Coronavirus Pneumonia (NCP) that emerge on 31st December 2019 from China and quickly became a Public Health Emergency of International Concern (PHEIC). In the absence of evidence-based proven prophylactic or therapeutic options, chloroquine/hydroxychloroquine (CQ/HCQ) patented as first line choice in COVID- 19 treatment, which raised concerns about drug poisoning, especially ocular toxicity. Objective: This study aims to investigate the possibility of ocular toxicity and the need for ophthalmic counseling to prescribing this therapeutic protocol. Methods: All the articles that were most relevant to the COVID-19 therapeutic or prophylactic options and CQ derivative ocular toxicity, were founded by a literature search and were thoroughly reviewed. Results: Anecdotal recent reports introduce CQ/HCQ as an effective therapeutic or prophylactic choice for COVID-19. Because of the short time prescribe and the insignificant cumulative dose of the drug on the one hand and a higher risk of cross-infection during an ophthalmic examination, on the other hand, an ophthalmologic consult is not recommended except in highrisk patients for retinal toxicity. Conclusion: This study recommended ophthalmic evaluation before CQ/HCQ prescription for treatment or prophylaxis of COVID-19 only in preexisting maculopathy.

Background: Acne is an infection of the skin that occurs in both men and women during their lifespan. There are various natural or synthetic products available in the market to prevent and cure this disease. Introduction: The majority of the world population depends on the herbs or natural resources for the relief of acne disease. These are used to lessen the cost of treatment and the side effects of synthetic analogs. Methods: We have explored the various authentic web resources to compile information regarding different patented and marketed herbal formulations for acne treatment. Results: It has been found that most of the herbal formulation for acne include the plant actives/extracts having the potential activity against the Propionibacterium acne. The occurrence of this skin disease is also associated with the presence of free radicals in the body, which also causes the inflammation and redness of the skin. Further, the study of various patents also revealed that herbs with anti-oxidant properties have been used in most of the herbal anti-acne formulations. Moreover, the various patents also give the idea that herbal formulations also prevent the appearance of pimples on the skin. Conclusion: It has been concluded that the herbal anti-acne formulation is not only used to treat acne but also prevents this disease safely and economically.

Aim: To design controlled release topical delivery of mupirocin for the treatment of skin infection. Background: Mupirocin is an antibacterial drug. Mupirocin works to kill the bacteria, which include strains of Staphylococcus aureus and Streptococcus pyogenes. It is also used for the treatment of inflammation of a hair follicle. The half-life of mupirocin is only 20-40 min. It has very slight solubility in water. Patent literature had shown work on ointment, antibiotic composition, nasal and topical composition. Emulgel is a duel control release system for the topical delivery of hydrophobic drugs. Objective: The objective was to formulate emulgel with controlled delivery of mupirocin using Sepineo P 600. Methods: Soya oil, tween 80 and polyethylene glycol 400 (Oil:Surfactant:Cosurfactant) were used for emulsion formulation. Emulgel was optimized by 32 factorial design. Sepineo P 600 and hydroxy propyl methyl cellulose K4M were used as independent variables. Drug excipient compatibility analysis was carried out by FTIR, UV and DSC spectra. Emulgel was evaluated for its physical characterization, in vitro release, ex vivo release, antimicrobial and anti-inflammatory study. Results: DSC, UV and FTIR analysis confirmed drug excipient compatibility. FE SEM showed a size range between 228-255 nm. Zeta potential was found to be -25.1 mV, which showed good stability of the emulsion. Design expert software showed F2 as an optimized batch. Release studies indicated that the controlled release of drugs forms Sepineo P 600 gel due to its higher gelling capacity. Batch F2 showed comparable results with marketed formulation against Staphylococcus aureus. For batch F2, 40 μg/ml was the minimal inhibitory concentration. Conclusion: Antimicrobial and anti-inflammatory study proved successful development of stably controlled release mupirocin emulgel.

Background: Malaria is a deadly disease. It is mostly treated using 4- aminoquinoline derivatives such as chloroquine etc. because it is well-tolerated, displays low toxicity, and after administration, it is rapidly absorbed. The combination of 4-aminoquinoline with other classes of antimalarial drugs has been reported to be an effective approach for the treatment of malaria. Furthermore, some patents reported hybrids 4-aminoquinolines containing ferrocene moiety with potent antimalarial activity. Objective: The objective of the current study is to prepare 4-aminoquinoline-ferrocene hybrids via esterification and amidation reactions. The compounds were characterized via FTIR, LC-MS and NMR spectroscopy. In vitro screening against chloroquine-sensitive P. falciparum parasite (NF54) at concentrations (1 μM and 5 μM) and an inhibitory concentration (full dose-response) was studied. Methods: The compounds were prepared via known reactions and monitored by Thin Layer Chromatography. The compounds were purified by column chromatography and characterized using FTIR, NMR and MS. In vitro antiplasmodial evaluation was performed against asexual parasite and chloroquine was used as a reference drug. Results: The percentage inhibition effects of the hybrid compounds were in a range of 97.9-102% at 5 μM and 36-96% at 1 μM. Furthermore, the IC50 values of the compounds were in the range of 0.7-1.6 μM when compared to the parent drug, 4-ferrocenylketobutanoic acid. Conclusion: The hybrid compounds displayed significant antimalarial activity when compared to the parent drug. However, they were not as effective as chloroquine on the drug-sensitive parasite. The findings revealed that 4-aminoquinolines and ferrocene are potential scaffolds for developing potent antimalarials.