Drugs acting on the renin-angiotensin-aldosterone system (RAAS) and deaths of COVID-19 patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are two of the most commonly used antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS). Previous research has shown that RAAS inhibitors increase the expression of angiotensin-converting enzyme, a cellular receptor for the severe acute respiratory syndrome coronavirus 2, raising concerns that the use of ACEi and ARBs in hypertensive patients may increase COVID-19 patient mortality. Therefore, the main aim of the current study was to find out the role of drugs acting on RAAS, particularly ACEi/ARBs in the deaths of COVID-19 patients. RESULTS: In total, 68 studies were found to be appropriate, reporting a total of 128,078 subjects. The odds ratio was found to be 1.14 [0.95, 1.36], which indicates the non-significant association of ACEi/ARBs with mortality of COVID-19 patients. Further, the association of individual ACEi/ARBs with mortality of COVID-19 patients was also found non-significant. The sensitivity analysis results have shown no significant effect of outliers on the outcome. CONCLUSIONS: Based on available evidence, ACEi/ARB were not significantly associated with deaths of COVID-19 patients.

Nanocarriers-Assisted Needle-Free Vaccine Delivery Through Oral and Intranasal Transmucosal Routes: A Novel Therapeutic Conduit

Drug delivery using oral route is the most popular, convenient, safest and least expensive approach. It includes oral transmucosal delivery of bioactive compounds as the mucosal cavity offers an intriguing approach for systemic drug distribution. Owing to the dense vascular architecture and high blood flow, oral mucosal layers are easily permeable and can be an ideal site for drug administration. Recently, the transmucosal route is being investigated for other therapeutic candidates such as vaccines for their efficient delivery. Vaccines have the potential to trigger immune reactions and can act as both prophylactic and therapeutic conduit to a variety of diseases. Administration of vaccines using transmucosal route offers multiple advantages, the most important one being the needle-free (non-invasive) delivery. Development of needle-free devices are the most recent and pioneering breakthrough in the delivery of drugs and vaccines, enabling patients to avoid needles, reducing anxiety, pain and fear as well as improving compliance. Oral, nasal and aerosol vaccination is a novel immunization approach that utilizes a nanocarrier to administer the vaccine. Nanocarriers improve the bioavailability and serve as adjuvants to elicit a stronger immune response, resulting in increased effectiveness of vaccination. Drugs and vaccines with lower penetration abilities can also be delivered transmucosally while maintaining their biological function. The development of micro/nanocarriers for transmucosal delivery of macromolecules, vaccines and other substances is currently drawing much attention and a number of studies were performed recently. This comprehensive review is aimed to summarize the most recent investigations on needle-free and non-invasive approaches for the delivery of vaccines using oral transmucosal route, their strengths and associated challenges. The oral transmucosal vaccine delivery by nanocarriers is the most upcoming advancement in efficient vaccine delivery and this review would help further research and trials in this field.

A Case Study: Analysis of Patents on Coronaviruses and Covid-19 for Technological Assessment and Future Research.

BACKGROUND: Protecting intellectual property rights are important and particularly pertinent for inventions that are an outcome of rigorous research and development. While the grant of patents is subject to establishing novelty and inventive step, it further indicates the technological development and is helpful for researchers working in the same technical domain. The aim of the present research work is to map the existing work through an analysis of patent literature in the field of Coronaviruses (CoV), particularly COVID-19 (2019-nCoV). CoV is a large family of viruses known to cause illness in humans and animals, particularly known for causing respiratory infections, as evidenced in earlier times, such as in MERS i.e., Middle East Respiratory Syndrome; and SRS i.e., Severe Acute Respiratory Syndrome. A recently identified novel-coronavirus, known as COVID-19, has caused pandemic situations across the globe. OBJECTIVE: To expand the analysis of patents related to CoV and 2019-nCoV, an evaluation has been conducted by patenting trends of particular strains of identified CoV diseases by present legal status, main concerned countries via the earliest priority years and its assignee types and inventors of identified relevant patents. The global patent documents were analyzed to check the scope of claims along with focuses and trends of the published patent documents for the entire CoV family, including 2019-nCoV through the present landscape. METHODS: To extract the results, the Derwent Innovation database was used by a combination of different keystrings. Approximately 3800 patents were obtained and further scrutinized and analyzed. The present write-up also discusses the recent progress of patent applications in a period of the year 2010 to 2020 (present) along with the recent developments in India for the treatment options for CoV and 2019-nCoV. RESULTS: Present analysis showed that key areas of the inventions were the vaccines and diagnostic kits apart from the composition for the treatment of CoV. It was also observed that no specific vaccine treatments are available for the treatment of 2019-nCov; however, developing novel chemical or biological drugs and kits for early diagnosis, prevention, and disease management is the primary governing topic among the patented inventions. The present study also indicates potential research opportunities for the future, particularly to combat 2019-nCoV. CONCLUSION: The present paper analyzes the existing patents in the field of Coronaviruses and 2019-nCoV and suggests a way forward for the effective contribution in this upcoming research area. From the trend analysis, an increase in the filing of the overall trend of patent families was observed for a period of 2010 to the current year. This multifaceted analysis of identified patent literature provides an understanding of the focuses on present ongoing research and a grey area in terms of the trends of technological innovations in disease management in patients with CoV and 2019-nCoV. Furthermore, the findings and outcome of the present study offer insights for the proposed research and innovation opportunities and provide actionable information in order to facilitate policymakers, academia, research-driven institutes and also investors to make better decisions regarding programmed steps for research and development for the diagnosis, treatment and taking preventive measures for CoV and 2019-nCoV. The present article also emphasizes the need for future development and the role of academia and collaboration with industry for speedy research with a rationale.

Antiviral Essential Oils Incorporated in Nanocarriers: Strategy for Prevention from COVID-19 and Future Infectious Pandemics.

BACKGROUND: Coronavirus has become a life-threatening disease and it is caused by severe acute respiratory syndrome (SARS). This new strain of coronavirus is not completely understood and to date, there is no treatment for coronavirus. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. In the meantime, guidelines of the ministry of AYUSH (Ayurveda, yoga, unani, siddha and homoepathy) include a traditional medicinal treatment for flu and fever and also recommended to boost immunity to prevent the spread of coronavirus. It is not possible to find which essential oil will offer the best level of protection. However, it is likely to assume that some essential oils are likely to offer a measurable level of defense in the same way they do with many other known viruses. METHODS: Literature relevant to various essential oils having antiviral activity has been collected and compiled. Various nanocarriers of essential oils have also been stated. The database was collected using various search engines such as J-Gate, Google Scholar, Sci-Hub, PubMed, ScienceDirect, etc. Results: Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activities and many more. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. CONCLUSION: Several essential oils possess potent antiviral activity and are characterized by fewer side effects and are safe for human use. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections. Lay Summary: Current COVID-19 era demands traditional treatment for immunity boost up as support therapy. Traditional ayurvedic medicines, mainly essential oils and Chinese herbs, have always played a vital role in the prevention and treatment of several epidemics and pandemics. Therefore, authors have summarized various essential oils having antiviral activity in current manuscript. Various nanocarriers of essential oils have been reported. Essential oils contain active constituents such as phenolic compounds, terpenoids, alkaloids, phenyl propanoids, etc., which are responsible for their biological properties such as antiviral, antibacterial, antimicrobial, antioxidant activity. However, the use of essential oils has always been limited due to poor solubility, solvent toxicity, volatility and low solubility. Many nanotechnology based carriers especially, liposomes, dendrimers, nanoparticles, nanoemulsion and microemulsion, etc. have been evidenced to overcome limitations associated with essential oils. The nanocarrier systems of these oils have proved the potential to treat viral and bacterial infections.

Nanotechnology Enabled Solutions to Combat Covid-19: Prevention, Treatment, and Diagnosis.

Changes in human lifestyles and environmental deterioration globally cause the emergence of new viruses, posing research challenges. The outburst of COVID-19 (nCoV19) is a recent example, wherein effective management of virus, using the conventional medication and effective diagnostic measures is a challenge. While many ongoing strategies from vaccine development to drug repurposing are currently being investigated, a targeted approach with nanotechnology can be helpful to meet the demand for preventive and diagnostic measures. The significant results of nanotechnology in providing better efficacy of pharmaceutical drugs is expected to combat nCoV19 by using nanotechnology- based solutions, preventive treatment, and diagnosis. This article addresses the dire need for nanotechnology-based solutions in the current pandemic, as well as analyzes the ongoing innovation and existing patents that can be used to provide better solutions. Multiple applications of nanotechnology are considered to be helpful in preventive and diagnostic measures, immune response modulation, and immunity boosters, along with projecting a pathway for industry and academic researchers for addressing such a pandemic.