COVID-19 Associated Thyroid Dysfunction and Other Comorbidities and Its Management Using Phytochemical-Based Therapeutics- A Natural Way.

The present severe acute respiratory syndrome-2 (SARS-CoV-2) mediated Coronavirus pandemic (COVID-19) and post-COVID-19 complications affect human life drastically. Patients who have been cured of COVID-19 infection are now experiencing post-COVID-19 associated comorbidities, which have increased mortality rates.  The SARS-CoV-2 infection distresses the lungs, kidneys, gastrointestinal tract, and various endocrine glands, including the thyroid. The emergence of variants which includes Omicron (B.1.1.529) and its lineages threaten the world severely. Among different therapeutic approaches, phytochemical-based therapeutics are not only cost-effective but also have lesser side effects. Recently a plethora of studies have shown the therapeutic efficacy of various phytochemicals for the treatment of COVID-19. Besides this, various phytochemicals have been found efficacious in treating several inflammatory diseases, including thyroid-related anomalies. The method of the phytochemical formulation is quick and facile and the raw materials for such herbal preparations are approved worldwide for human use against certain disease conditions. Owing to the advantages of phytochemicals, this review primarily discusses the COVID-19-related thyroid dysfunction and the role of key phytochemicals to deal with thyroid anomaly and post-COVID-19 complications. Further, this review shed light on the mechanism via which COVID-19 and its related complication affect organ function of the body, along with the mechanistic insight into the way by which phytochemicals could help to cure post-COVID-19 complications in thyroid patients. Considering the advantages offered by phytochemicals as a safer and cost-effective medication they can be potentially used to combat COVID-19-associated comorbidities.

Internet-of-medical-things integrated point-of-care biosensing devices for infectious diseases: Toward better preparedness for futuristic pandemics.

Microbial pathogens have threatened the world due to their pathogenicity and ability to spread in communities. The conventional laboratory-based diagnostics of microbes such as bacteria and viruses need bulky expensive experimental instruments and skilled personnel which limits their usage in resource-limited settings. The biosensors-based point-of-care (POC) diagnostics have shown huge potential to detect microbial pathogens in a faster, cost-effective, and user-friendly manner. The use of various transducers such as electrochemical and optical along with microfluidic integrated biosensors further enhances the sensitivity and selectivity of detection. Additionally, microfluidic-based biosensors offer the advantages of multiplexed detection of analyte and the ability to deal with nanoliters volume of fluid in an integrated portable platform. In the present review, we discussed the design and fabrication of POCT devices for the detection of microbial pathogens which include bacteria, viruses, fungi, and parasites. The electrochemical techniques and current advances in this field in terms of integrated electrochemical platforms that include mainly microfluidic- based approaches and smartphone and Internet-of-things (IoT) and Internet-of-Medical-Things (IoMT) integrated systems have been highlighted. Further, the availability of commercial biosensors for the detection of microbial pathogens will be briefed. In the end, the challenges while fabrication of POC biosensors and expected future advances in the field of biosensing have been discussed. The integrated biosensor-based platforms with the IoT/IoMT usually collect the data to track the community spread of infectious diseases which would be beneficial in terms of better preparedness for current and futuristic pandemics and is expected to prevent social and economic losses.

Biosensors based detection of novel biomarkers associated with COVID-19: Current progress and future promise.

The pandemic situation of COVID-19 has caused global alarm in health care, devastating loss of lives, strangled economy, and paralysis of normal livelihood. The high inter-individual transmission rate created havoc in the global community. Although tremendous efforts are pitching in from across the globe to understand this disease, the clinical features seemed to have a wide range including fever, cough, and fatigue are the prominent features. Congestion, rhinorrhea, sore throat, and diarrhea are other less common features observed. The challenge of this disease lies in the difficulty in maneuvering the clinical course causing severe complications. One of the major causative factors for multi-organ failure in patients with severe COVID-19 complications is systemic vasculitis and cytokine-mediated coagulation disorders. Hence, effective markers trailing the disease severity and disease prognosis are urgently required for prompt medical treatment. In this review article, we have emphasized currently identified inflammatory, hematological, immunological, and biochemical biomarkers of COVID-19. We also discussed currently available biosensors for the detection of COVID-19-associated biomarkers & risk factors and the detection methods as well as their performances. These could be effective tools for rapid and more promising diagnoses in the current pandemic situation. Effective biomarkers and their rapid, scalable, & sensitive detection might be beneficial for the prevention of serious complications and the clinical management of the disease.

Clinically available/under trial drugs and vaccines for treatment of SARS-COV-2

Prior 2019 to work date entire world is seriously influenced by an appalling illness called COVID sickness [Coronavirus disease-2019 (COVID-19)] which is brought about by another strain of coronavirus known as severe acute respiratory syndrome-Coronavirus-2. This pandemic was first seen in the Hubei area in Wuhan city of China. To date above 170 million individuals have been influenced by this infection and more than 3 million individuals died. The race of finding specific therapeutic drugs and efficacious vaccine candidates is still going on to tackle the pandemic-associated morbidities. This chapter discussed different clinically accessible medications (remdesivir, hydroxychloroquine, azithromycin, etc.) and immunizations (mRNA-1273, Sputanik, Pfizer, etc.) which are either in use or under trial for the treatment of COVID-19.

3D printed human organoids: High throughput system for drug screening and testing in current COVID-19 pandemic.

In the current pandemic, scenario the world is facing a huge shortage of effective drugs and other prophylactic medicine to treat patients which created havoc in several countries with poor resources. With limited demand and supply of effective drugs, researchers rushed to repurpose the existing approved drugs for the treatment of COVID-19. The process of drug screening and testing is very costly and requires several steps for validation and treatment efficacy evaluation ranging from in-vitro to in-vivo setups. After these steps, a clinical trial is mandatory for the evaluation of treatment efficacy and side effects in humans. These processes enhance the overall cost and sometimes the lead molecule show adverse effects in humans and the trial ends up in the final stages. Recently with the advent of three-dimensional (3D) organoid culture which mimics the human tissue exactly the process of drug screening and testing can be done in a faster and cost-effective manner. Further 3D organoids prepared from stems cells taken from individuals can be beneficial for personalized drug therapy which could save millions of lives. This review discussed approaches and techniques for the synthesis of 3D-printed human organoids for drug screening. The key findings of the usage of organoids for personalized medicine for the treatment of COVID-19 have been discussed. In the end, the key challenges for the wide applicability of human organoids for drug screening with prospects of future orientation have been included.

Microfluidics-Based Point-of-Care Testing (POCT) Devices in Dealing with Waves of COVID-19 Pandemic: The Emerging Solution.

Recent advances in microfluidics-based point-of-care testing (POCT) technology such as paper, array, and beads have shown promising results for diagnosing various infectious diseases. The fast and timely detection of viral infection has proven to be a critical step for deciding the therapeutic outcome in the current COVID-19 pandemic, which in turn not only enhances the patient survival rate but also reduces the disease-associated comorbidities. In the present scenario, rapid, noninvasive detection of the virus using low cost and high throughput microfluidics-based POCT devices embraces the advantages over existing diagnostic technologies, for which a centralized lab facility, expensive instruments, sample pretreatment, and skilled personnel are required. Microfluidic-based multiplexed POCT devices can be a boon for clinical diagnosis in developing countries that lacks a centralized health care system and resources. The microfluidic devices can be used for disease diagnosis and exploited for the development and testing of drug efficacy for disease treatment in model systems. The havoc created by the second wave of COVID-19 led several countries' governments to the back front. The lack of diagnostic kits, medical devices, and human resources created a huge demand for a technology that can be remotely operated with single touch and data that can be analyzed on a phone. Recent advancements in information technology and the use of smartphones led to a paradigm shift in the development of diagnostic devices, which can be explored to deal with the current pandemic situation. This review sheds light on various approaches for the development of cost-effective microfluidics POCT devices. The successfully used microfluidic devices for COVID-19 detection under clinical settings along with their pros and cons have been discussed here. Further, the integration of microfluidic devices with smartphones and wireless network systems using the Internet-of-things will enable readers for manufacturing advanced POCT devices for remote disease management in low resource settings.

Phytochemicals-based targeting RdRp and main protease of SARS-CoV-2 using docking and steered molecular dynamic simulation: A promising therapeutic approach for Tackling COVID-19.

The ongoing COVID-19 pandemic has affected millions of people worldwide and caused substantial socio-economic losses. Few successful vaccine candidates have been approved against SARS-CoV-2; however, their therapeutic efficacy against the mutated strains of the virus remains questionable. Furthermore, the limited supply of vaccines and promising antiviral drugs have created havoc in the present scenario. Plant-based phytochemicals (bioactive molecules) are promising because of their low side effects and high therapeutic value. In this study, we aimed to screen for suitable phytochemicals with higher therapeutic value using the two most crucial proteins of SARS-CoV-2, the RNA-dependent RNA polymerase (RdRp) and main protease (Mpro). We used computational tools such as molecular docking and steered molecular dynamics simulations to gain insights into the different types of interactions and estimated the relative binding forces between the phytochemicals and their respective targets. To the best of our knowledge, this is the first report that not only involves a search for a therapeutic bioactive molecule but also sheds light on the mechanisms underlying target inhibition in terms of calculations of force and work needed to extractthe ligand from the pocket of its target. The complexes showing higher binding forces were subjected to 200 ns molecular dynamic simulations to check the stability of the ligand inside the binding pocket. Our results suggested that isoskimmiwallin and terflavin A are potential inhibitors of RdRp, whereas isoquercitrin and isoorientin are the lead molecules against Mpro. Collectively, our findings could potentially aid in the development of novel therapeutics against COVID-19.

High throughput molecularly imprinted polymers based electrochemical nanosensors for point-of-care diagnostics of COVID-19.

The importance of early diagnosis of infectious disease has been revealed well by the COVID-19 pandemic. The current methods for testing SARS-CoV-2 mainly utilize biorecognition elements. The process of production of these biorecognition elements is not only tedious, time-consuming but also costly. The molecularly imprinted polymers recently have gained considerable attention as they are stable and also offer high selectivity and specificity than conventional labels. The present review discussed the MIPs-based electrochemical nano-sensors diagnostic of SARS-CoV-2.

Immunoinformatics and molecular modeling approach to design universal multi-epitope vaccine for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable and pathogenic human coronavirus that caused a pandemic situation of acute respiratory syndrome, called COVID-19, which has posed a significant threat to global health security. The aim of the present study is to computationally design an effective peptide-based multi-epitope vaccine (MEV) against SARS-CoV-2. The overall model quality of the vaccine candidate, immunogenicity, allergenicity, and physiochemical analysis have been conducted and validated. Molecular dynamics studies confirmed the stability of the candidate vaccine. The docked complexes during the simulation revealed a strong and stable binding interactions of MEV with human and mice toll-like receptors (TLR), TLR3 and TLR4. Finally, candidate vaccine codons have been optimized for their in silico cloning in E. coli expression system, to confirm increased expression. The proposed MEV can be a potential candidate against SARS-CoV-2, but experimental validation is needed to ensure its safety and immunogenicity status.

Point-of-Care Biosensor-Based Diagnosis of COVID-19 Holds Promise to Combat Current and Future Pandemics.

Efficient and rapid detection of viruses plays an extremely important role in disease prevention, diagnosis, and environmental monitoring. Early screening of viral infection among the population has the potential to combat the spread of infection. However, the traditional methods of virus detection being used currently, such as plate culturing and quantitative RT-PCR, give promising results, but they are time-consuming and require expert analysis and costly equipment and reagents; therefore, they are not affordable by people in low socio-economic groups in developing countries. Further, mass or bulk testing chosen by many governments to tackle the pandemic situation has led to severe shortages of testing kits and reagents and hence are affecting the demand and supply chain drastically. We tried to include all the reported current scenario-based biosensors such as electrochemical, optical, and microfluidics, which have the potential to replace mainstream diagnostic methods and therefore could pave the way to combat COVID-19. Apart from this, we have also provided information on commercially available biosensors for detection of SARS-CoV-2 along with the challenges in development of better diagnostic approaches. It is therefore expected that the content of this review will help researchers to design and develop more sensitive advanced commercial biosensor devices for early diagnosis of viral infection, which can open up avenues for better and more specific therapeutic outcomes.