A Systematic Review of Clinical Pharmacokinetics of Inhaled Antiviral.

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections.

Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature.

Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body's defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress, declining the expression of the ACE-2 receptor, lowering the discharge of pro-inflammatory substances, and inhibiting the 3CLPro (main protease) and PLpro enzyme of SARS-CoV-2. The data of clinical studies, inventive compositions, and patent literature revealed that selenium monotherapy and its compositions with other nutritional supplements/drugs (vitamin, iron, zinc, copper, ferulic acid, resveratrol, spirulina, N-acetylcysteine, fish oil, many herbs, doxycycline, azithromycin, curcumin, quercetin, etc.,) might be practical to prevent/treat COVID-19. The studies have also suggested a correlation between COVID-19 and selenium deficiency. This indicates that adequate selenium supplementation may provide promising treatment outcomes in COVID-19 patients. The authors foresee the development and commercialization of Selenium-based compositions and dosage forms (spray, inhalers, control release dosage forms, etc.) to battle COVID-19. We also trust that numerous selenium-based compositions are yet to be explored. Accordingly, there is good scope for scientists to work on developing novel and inventive selenium-based compositions to fight against COVID-19. However, there is also a need to consider the narrow therapeutic window and chemical interaction of selenium before developing selenium-based compositions.

Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature

Selenium is an indispensable trace element for all living organisms. It is an essential structural component of several selenium-dependent enzymes, which support the human body’s defense mechanism. Recently, the significance of selenium in preventing/treating COVID-19 has been documented in the literature. This review highlights the clinical studies, compositions, and patent literature on selenium to prevent/treat COVID-19. Selenium exerts its anti-COVID-19 action by reducing oxidative stress, declining the expression of the ACE-2 receptor, lowering the discharge of pro-inflammatory substances, and inhibiting the 3CLPro (main protease) and PLpro enzyme of SARS-CoV-2. The data of clinical studies, inventive compositions, and patent literature revealed that selenium monotherapy and its compositions with other nutritional supplements/drugs (vitamin, iron, zinc, copper, ferulic acid, resveratrol, spirulina, N-acetylcysteine, fish oil, many herbs, doxycycline, azithromycin, curcumin, quercetin, etc.,) might be practical to prevent/treat COVID-19. The studies have also suggested a correlation between COVID-19 and selenium deficiency. This indicates that adequate selenium supplementation may provide promising treatment outcomes in COVID-19 patients. The authors foresee the development and commercialization of Selenium-based compositions and dosage forms (spray, inhalers, control release dosage forms, etc.) to battle COVID-19. We also trust that numerous selenium-based compositions are yet to be explored. Accordingly, there is good scope for scientists to work on developing novel and inventive selenium-based compositions to fight against COVID-19. However, there is also a need to consider the narrow therapeutic window and chemical interaction of selenium before developing selenium-based compositions.

A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak.

Monkeypox disease (MPX) is currently considered a global threat after COVID-19. European Medicines Agency (EMA) approved Tecovirimat in capsule dosage form (200 mg) as the first treatment for MPX in January 2022. This article highlights Tecovirimat's development and patent literature review and is believed to benefit the scientists working on developing MPX treatments. The literature for Tecovirimat was gathered from the website of SIGA Technologies (developer of Tecovirimat), regulatory agencies (EMA, United States Food and Drug Administration (USFDA), and Health Canada), PubMed, and freely accessible clinical/patent databases. Tecovirimat was first recognized as an anti-orthopoxvirus molecule in 2002 and developed by SIGA Technologies. The USFDA and Health Canada have also recently approved Tecovirimat to treat smallpox in 2018 and 2021, respectively. The efficacy of Tecovirimat was verified in infected non-human primates (monkeys) and rabbits under the USFDA's Animal Rule. Most clinical studies have been done on Tecovirimat's safety and pharmacokinetic parameters. The patent literature has revealed inventions related to the capsule, injection, suspension, crystalline forms, amorphous form, and drug combinations (Tecovirimat + cidofovir) and process for preparing Tecovirimat. The authors foresee the off-label use of Tecovirimat in the USA and Canada for MPX and other orthopoxvirus infections. The authors also trust that there is immense scope for developing new Tecovirimat-based treatments (new drug combinations with other antivirals) for orthopoxvirus and other viral diseases. Drug interaction studies and drug resistance studies on Tecovirimat are also recommended. Tecovirimat is believed to handle the current MPX outbreak and is a new hope of biosecurity against smallpox or orthopoxvirus-related bioterrorism attack.

The Therapeutic and Prophylactic Potential of Quercetin against COVID-19: An Outlook on the Clinical Studies, Inventive Compositions, and Patent Literature.

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.

Nigella sativa L. and COVID-19: A Glance at The Anti-COVID-19 Chemical Constituents, Clinical Trials, Inventions, and Patent Literature.

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future.

Burden of COVID-19: a preliminary analysis in the population of Saudi Arabia.

Background: Coronavirus infection (COVID-19) has resulted in an unprecedented number of human deaths and economic losses. Analyzing the role of disease in different groups of people is useful for determining the burden of disease. As a result, the purpose of this study was to investigate the influence of COVID-19 on the Saudi Arabian population's quality of life, with a particular emphasis on the likely fall in their life expectancy. Methods: A cross-sectional and retrospective analysis of 2,988 patients' databases was performed to assess COVID-19-induced mortality and complications in the community. The data was gathered from official websites that track the disease's impact daily between July and October 2021. On the acquired data, disability-adjusted life years (DALYs) and relative risk analysis were performed. The data was statistically analyzed using SPSS IBM 25. The Pearson's correlation test was used to examine the relationship between age and disease impact. The significance of the findings was determined by using a P value of less than 0.05. Results: The data from the study indicated that the positive test rate, infection rate, and mortality rate in the population were 1.84% [+0.11/-0.39 of 95% confidence interval (CI)], 1.54% (+0.38/-0.52 of CI), and 1.59% (+0.4/-0.7 of CI), respectively. Highest percentage of mortality was observed in Riyadh (17%), followed by Jeddah (8.7%) and Makkah (7.5%). The DALYs/100,000 inhabitants increased progressively as the age of the population increased, and the highest value was found for those over 70 years old (25.73 ± 2.09). Similarly, the risk outcome (55%) increased significantly (p = 0.037) from 40 years onwards, and the maximum was observed at above 70 years (184%, p = 0.006). The correlation analysis indicated a significant association (p = 0.032) between age and COVID-19 induced mortality from the 40-year-old population onwards. Conclusion: The current study found that the COVID-19 load in Saudi Arabia was comparable to that in nations that were said to have performed well during the pandemic. DALYs increased from 40 years to 60 years, although people over 60 years had a lower life expectancy and were more susceptible to infection. After 60 years, the occurrence of numerous co-morbid illnesses may have added to the population's burden of COVID-19. Further research in this area may yield a more precise estimate of the COVID-19-induced burden on the entire population.

Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review.

An unprecedented global health crisis has developed due to the emergence of the mysterious coronavirus-2 of the severe acute respiratory syndrome, which has resulted in millions of deaths around the globe, as no therapy could control the 'cytokine storm'. Consequently, many vaccines have been developed and several others are being developed for this infection. Although most of the approved vaccines have been highly effective, many developing, and economically poor countries are still deprived of vaccination against SARS-CoV-2 due to the unequal distribution of vaccines worldwide. Furthermore, the uncertainty about the effectiveness of the available vaccines against the emerging mutants and variants also remains a matter of concern. Due to the multistep pathogenesis and unique features, combination therapy using safe immunomodulatory and antiviral drugs should be considered as the most effective and acceptable therapeutic regimen for this infection. Based on a thorough assessment of the literature, it was determined that it would be interesting to study the therapeutic potential of ivermectin and doxycycline, given their roles in several biological pathways involved in SARS CoV-2 pathogenesis. Following that, a comprehensive literature search was undertaken using Scopus, Web of Science, and Pubmed, depending on the inclusion and exclusion criteria. The present study provides a mechanism and comprehensive report, highlighting the role of combined therapy with ivermectin and doxycycline in alleviating the 'cytokine storm' of COVID-19 infection.

Development of Therapeutic and Prophylactic Zinc Compositions for Use against COVID-19: A Glimpse of the Trends, Inventions, and Patents.

Zinc is an essential nutrient for human health; it is involved in the catalytic, structural, and regulatory functions of the human cellular system. Different compositions of zinc, as well as its pharmaceutically acceptable salts, are available on the market. Recent studies have demonstrated the role of zinc in combating COVID-19. It has been determined that zinc prevents the entry of SARS-CoV-2 into cells by lowering the expression of ACE-2 receptors and inhibiting the RNA-dependent RNA polymerase of SARS-CoV-2. Zinc also prevents the cytokine storm that takes place after the entry of SARS-CoV-2 into the cell, via its anti-inflammatory activity. The authors believe that no study has yet been published that has reviewed the trends, inventions, and patent literature of zinc compositions to treat/prevent COVID-19. Accordingly, this review has been written in order to fill this gap in the literature. The information about the clinical studies and the published patents/patent applications was retrieved from different databases. This review covers patent literature on zinc compositions up to 31 January 2022. Many important patents/patent applications for zinc-based compositions filed by innovative universities and industries were identified. The patent literature revealed zinc compositions in combination with zinc ionophores, antioxidants, antivirals, antibiotics, hydroxychloroquine, heparin, ivermectin, and copper. Most of these studies were supported by clinical trials. The patent literature supports the potential of zinc and its pharmaceutical compositions as possible treatments for COVID-19. The authors believe that countless zinc-based compositions are still unexplored, and there is an immense opportunity to evaluate a considerable number of the zinc-based compositions for use against COVID-19.

Epidemiological determinants for the spread of COVID-19 in Riyadh Province of Saudi Arabia.

BACKGROUND AND OBJECTIVE: Coronavirus Disease 2019 (COVID-19) has affected millions of individuals all over the world. In addition to the patients' compelling indications, various sociodemographic characteristics were identified to influence infection complications. The purpose of this study was to assess the impact of the aforementioned parameters on the dissemination of COVID-19 among residents of Saudi Arabia's Riyadh region. MATERIALS AND METHODS: In the Saudi Arabian province of Riyadh, a cross-sectional retrospective analysis of COVID-19 incidences, recoveries, and case-fatality ratio (CFR) was undertaken. The study was carried out by gathering daily COVID-19 records from the ministry of health's official websites between October 2020 and September 2021. The influencing factors were obtained from the statistical authority. Using the SPSS IBM 25 software, the data was examined. The association between demographic factors as well as the presence of comorbidity on the COVID-19 outcome was determined using Spearman's correlation and regression tests. P < 0.05 was considered to indicate the significance of the results. RESULTS: The data from the study indicated that the highest number of COVID-19 cases were recorded in June 2021, and peak recovery was observed in July 2021. The CFR declined progressively from October 2020 to just over 1, even when the cases peaked. A significant (p < 0.05) correlation between diabetes and COVID-19 incidences was observed. The recovery rate had a significant (p < 0.05) association with the literacy rate and those aged 14-49 years old. Presences of co-morbidities such as Dyslipidemia, hypertension, diabetes, asthma, stroke and heart failure have negatively affected the recovery from COVID-19 in the population. The CFR is significantly (p < 0.05) associated with people over 60, hypertensive patients, and asthma patients. Regression analysis suggested that the risk of complications due to COVID-19 infection is more in males, people above 60 years age and those suffering from co-morbidities. CONCLUSIONS: The findings of the study indicate an association between several of the characteristics studied, such as gender, age, and comorbidity, and the spread of infection, recovery, and mortality. To restrict the spread of COVID-19 and prevent its complications, effective measures are required to control the modifiable risk factors.

Insight into the biological impact of COVID-19 and its vaccines on human health.

COVID-19 (coronavirus disease-2019) is a contagious illness that has been declared a global epidemic by the World Health Organization (WHO). The coronavirus causes diseases ranging in severity from the common cold to severe respiratory diseases and death. Coronavirus primarily affects blood pressure by attaching to the angiotensin converting enzyme 2 (ACE 2) receptor. This virus has an impact on multiple organ systems, including the central nervous system, immune system, cardiovascular system, peripheral nervous system, gastrointestinal tract, endocrine system, urinary system, skin, and pregnancy. For the prevention of COVID-19, various vaccines such as viral-like particle vaccines, entire inactivated virus vaccines, viral vector vaccines, live attenuated virus vaccines, subunit vaccines, RNA vaccines, and DNA vaccines are now available. Some of the COVID-19 vaccines are reported to cause a variety of adverse effects that range from mild to severe in nature. SARS-CoV-2 replication is controlled by the RNA-Dependent RNA-Polymerase enzyme (RdRp). The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use. Galidesivir's in vitro and in vivo activities are limited to RNA of human public health concern. Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body from their harmful effects and to provide options for making better choices in a timely manner.

A Patent Review on the Therapeutic Application of Monoclonal Antibodies in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains spike proteins that assist the virus in entering host cells. In the absence of a specific intervention, efforts are afoot throughout the world to find an effective treatment for SARS-CoV-2. Through innovative techniques, monoclonal antibodies (MAbs) are being designed and developed to block a particular pathway of SARS-CoV-2 infection. More than 100 patent applications describing the development of MAbs and their application against SARS-CoV-2 have been registered. Most of them target the receptor binding protein so that the interaction between virus and host cell can be prevented. A few monoclonal antibodies are also being patented for the diagnosis of SARS-CoV-2. Some of them, like Regeneron® have already received emergency use authorization. These protein molecules are currently preferred for high-risk patients such as those over 65 years old with compromised immunity and those with metabolic disorders such as obesity. Being highly specific in action, monoclonal antibodies offer one of the most appropriate interventions for both the prevention and treatment of SARS-CoV-2. Technological advancement has helped in producing highly efficacious MAbs. However, these agents are known to induce immunogenic and non-immunogenic reactions. More research and testing are required to establish the suitability of administering MAbs to all patients at risk of developing a severe illness. This patent study is focused on MAbs as a therapeutic option for treating COVID-19, as well as their invention, patenting information, and key characteristics.

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19.

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.