Recent Advances in Understanding SARS-CoV-2 Infection and Updates on Potential Diagnostic and Therapeutics for COVID-19

A more focused approach is needed to understand the SARS-CoV-2 virulence, structure, and genomics to devise more effective diagnostic and treatment interventions as this virus can evade the immune attack and causes life-threatening complications such as cytokine storm. The spread of the virus is still amplifying and causing thousands of new cases worldwide. It is essential to review current diagnostics and treatment approaches to pave the way to correct or modify our current practices to make more effective interventions against COVID-19. COVID-19 vaccine development has moved at a breakneck pace since the outbreak began, utilizing practically all possible platforms or tactics to ensure the success of vaccines. A total of 42 vaccine candidates have already entered clinical trials, including promising results from numerous vaccine candidates in phase 1 or phase 2 trials. Further, many existing drugs are being explored on broad-spectrum antiviral medications for their use in clinical recovery against COVID-19. The present review attempts to re-examine the SARS-CoV-2 structure, its viral life cycle, clinical symptoms and pathogenesis, mode of transmission, diagnostics, and treatment strategies that may be useful for resorting to more effective approaches for controlling COVID-19. Various antiviral drugs and vaccination strategies with their strengths and weaknesses are also discussed in the paper to augment our understanding of COVID-19 management.Copyright © 2022 Bentham Science Publishers.

Treatment Methods and Vaccine Alternatives of COVID-19

COVID-19, which is triggered by the new SARS-CoV-2 virus, is the main reason of mortality in the whole world. This virus outbreak has clearly demonstrated that it is a pandemic. The global COVID-19 outbreak has galvanized whole scientific community to join forces in the fight against this viral threat. Scientists and huge pharmaceutical companies are working around the clock to discover a cure. This project consists of two parts: first, testing current medications against the COVID-19 onslaughts and second, developing, testing, and manufacturing a harmless and efficacious vaccination as a long-term solution for the pandemic. At the end of October 2020 COVID-19 had approximately 39000000 cases around the world with almost 1100000 deaths around the globe. Fever, cough, sore throat, anosmia, difficulty breathing and myalgia are some of the symptoms. There is evidence of immune cells migrating to damaged organs, resulting in overproduction of proinflammatory cytokines that help in the illness process and make the immune system a key component in the COVID-19 infection illness process. The first clinical trials for Hydroxychloroquine (HCQ), a promising medication, have been halted. The FDA then approved the use of recovered COVID-19 individuals with the same blood group's convalescent serum as a therapeutic option. Research is going on a number of possible vaccine candidates containing monoclonal antibody as method of eradicating this viral spread. The motive of this article is to review the recent pharmacological therapies under trial and the various vaccine candidates in development to stop this global pandemic.

Chemical Sensor Nanotechnology in Pharmaceutical Drug Research.

The increase in demand for pharmaceutical treatments due to pandemic-related illnesses has created a need for improved quality control in drug manufacturing. Understanding the physical, biological, and chemical properties of APIs is an important area of health-related research. As such, research into enhanced chemical sensing and analysis of pharmaceutical ingredients (APIs) for drug development, delivery and monitoring has become immensely popular in the nanotechnology space. Nanomaterial-based chemical sensors have been used to detect and analyze APIs related to the treatment of various illnesses pre and post administration. Furthermore, electrical and optical techniques are often coupled with nano-chemical sensors to produce data for various applications which relate to the efficiencies of the APIs. In this review, we focus on the latest nanotechnology applied to probing the chemical and biochemical properties of pharmaceutical drugs, placing specific interest on several types of nanomaterial-based chemical sensors, their characteristics, detection methods, and applications. This study offers insight into the progress in drug development and monitoring research for designing improved quality control methods for pharmaceutical and health-related research.

An outlook on potential protein targets of COVID-19 as a druggable site.

BACKGROUND: SARS-CoV-2 which causes COVID-19 disease has started a pandemic episode all over the world infecting millions of people and has created medical and economic crisis. From December 2019, cases originated from Wuhan city and started spreading at an alarming rate and has claimed millions of lives till now. Scientific studies suggested that this virus showed genomic similarity of about 90% with SARS-CoV and is found to be more contagious as compared to SARS-CoV and MERS-CoV. Since the pandemic, virus has undergone constant mutation and few strains have raised public concern like Delta and Omicron variants of SARS-CoV-2. OBJECTIVE: This review focuses on the structural features of SARS-CoV-2 proteins and host proteins as well as their mechanism of action. We have also elucidated the repurposed drugs that have shown potency to inhibit these protein targets in combating COVID-19. Moreover, the article discusses the vaccines approved so far and those under clinical trials for their efficacy against COVID-19. CONCLUSION: Using cryo-electron microscopy or X-ray diffraction, hundreds of crystallographic data of SARS-CoV-2 proteins have been published including structural and non-structural proteins. These proteins have a significant role at different aspects in the viral machinery and presented themselves as potential target for drug designing and therapeutic interventions. Also, there are few host cell proteins which helps in SARS-CoV-2 entry and proteolytic cleavage required for viral infection.

Antiviral Peptides (AVPs) of Marine Origin as Propitious Therapeutic Drug Candidates for the Treatment of Human Viruses.

The marine environment presents a favorable avenue for potential therapeutic agents as a reservoir of new bioactive natural products. Due to their numerous potential pharmacological effects, marine-derived natural products-particularly marine peptides-have gained considerable attention. These peptides have shown a broad spectrum of biological functions, such as antimicrobial, antiviral, cytotoxic, immunomodulatory, and analgesic effects. The emergence of new virus strains and viral resistance leads to continuing efforts to develop more effective antiviral drugs. Interestingly, antimicrobial peptides (AMPs) that possess antiviral properties and are alternatively regarded as antiviral peptides (AVPs) demonstrate vast potential as alternative peptide-based drug candidates available for viral infection treatments. Hence, AVPs obtained from various marine organisms have been evaluated. This brief review features recent updates of marine-derived AVPs from 2011 to 2021. Moreover, the biosynthesis of this class of compounds and their possible mechanisms of action are also discussed. Selected peptides from various marine organisms possessing antiviral activities against important human viruses-such as human immunodeficiency viruses, herpes simplex viruses, influenza viruses, hepatitis C virus, and coronaviruses-are highlighted herein.

Drug-based therapeutic strategies for COVID-19-infected patients and their challenges.

Emerging epidemic-prone diseases have introduced numerous health and economic challenges in recent years. Given current knowledge of COVID-19, herd immunity through vaccines alone is unlikely. In addition, vaccination of the global population is an ongoing challenge. Besides, the questions regarding the prevalence and the timing of immunization are still under investigation. Therefore, medical treatment remains essential in the management of COVID-19. Herein, recent advances from beginning observations of COVID-19 outbreak to an understanding of the essential factors contributing to the spread and transmission of COVID-19 and its treatment are reviewed. Furthermore, an in-depth discussion on the epidemiological aspects, clinical symptoms and most efficient medical treatment strategies to mitigate the mortality and spread rates of COVID-19 is presented.

Recent advances in potential drug therapies combating COVID-19 and related coronaviruses-A perspective.

Coronaviruses (CoVs) are a large family of viruses responsible for the severe pathophysiological effects on human health. The most severe outbreak includes Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 poses major challenges to clinical management because no specific FDA-approved therapy yet to be available. Thus, the existing therapies are being used for the treatment of COVID-19, which are under clinical trials and compassionate use, based on in vitro and in silico studies. In this review, we summarize the potential therapies utilizing small molecules, bioactive compounds, nucleoside and nucleotide analogs, peptides, antibodies, natural products, and synthetic compounds targeting the complex molecular signaling network involved in COVID-19. In this review＞230 natural and chemically synthesized drug therapies are described with their recent advances in research and development being done in terms of their chemical, structural and functional properties. This review focuses on possible targets for viral cells, viral proteins, viral replication, and different molecular pathways for the discovery of novel viral- and host-based therapeutic targets against SARS-CoV-2.

A Bioluminescent Biosensor for Quantifying the Interaction of SARS-CoV-2 and Its Receptor ACE2 in Cells and In Vitro.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus-host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus-cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery process.

Towards Goals to Refine Prophylactic and Therapeutic Strategies Against COVID-19 Linked to Aging and Metabolic Syndrome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gave rise to the coronavirus disease 2019 (COVID-19) pandemic. A strong correlation has been demonstrated between worse COVID-19 outcomes, aging, and metabolic syndrome (MetS), which is primarily derived from obesity-induced systemic chronic low-grade inflammation with numerous complications, including type 2 diabetes mellitus (T2DM). The majority of COVID-19 deaths occurs in people over the age of 65. Individuals with MetS are inclined to manifest adverse disease consequences and mortality from COVID-19. In this review, we examine the prevalence and molecular mechanisms underlying enhanced risk of COVID-19 in elderly people and individuals with MetS. Subsequently, we discuss current progresses in treating COVID-19, including the development of new COVID-19 vaccines and antivirals, towards goals to elaborate prophylactic and therapeutic treatment options in this vulnerable population.

A review on the clinical trials of repurposing therapeutic drugs, mechanisms and preventive measures against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly transmittable pathogenic viral infection that causes a disease known as COVID-19. It is a pandemic and public health challenge ravaging the world today. Unfortunately, with the daily increase of infected individuals, there is no known drug approved for the treatment of COVID-19. However, there are therapeutic drugs with the potentials to inhibit endocytic pathways, suppress ribonucleic acid (RNA) polymerase activities, and reduce the replication of SARS-CoV-2. These drugs modifications are aimed at reducing inflammation, time of recovery, and number of deaths. This review is aimed at providing updated information on the clinical manifestations, diagnosis, preventive measures and therapeutic drugs used against SARS-CoV-2. The finding of this review revealed that some of these drugs are transmembrane protease, serine 2, and angiotensin-converting enzyme 2 inhibitors with the capacity to block the entrance/replication of SARS-CoV-2 in a host cell and therefore, may be promising in preventing the spread and mortality of SARS-CoV-2. However, these drugs may cause detrimental health effects such as toxic and non-efficacy issues. Therefore great caution should be employed by health professionals when prescribing these drugs to COVID-19 patients.

Mechanistic insight into anti-COVID-19 drugs: recent trends and advancements.

The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) has been established now to be a deadly disease afflicting the whole world with worst consequences on healthcare, economy and day-to-day life activities. Being a communicable disease, which is highly pathogenic in humans, causing cough, throat infection, breathing problems, high fever, muscle pain, and may lead to death in some cases especially those having other comorbid conditions such as heart or kidney problems, and diabetes. Finding an appropriate drug and vaccine candidate against coronavirus disease (COVID-19) remains an ultimate and immediate goal for the global scientific community. Based on previous studies in the literature on SARS-CoV infection, there are a number of drugs that may inhibit the replication of SARS-CoV-2 and its infection. Such drugs comprise of inhibitors of Angiotensin-Converting Enzyme 2 (ACE2), transmembrane Serine Protease 2 (TMPRSS2), nonstructural protein 3C-like protease, nonstructural RNA-dependent RNA polymerase (RdRp) and many more. The antiviral drugs such as chloroquine and hydroxychloroquine, lopinavir and ritonavir as inhibitors for HIV protease, nucleotide analogue remdesivir, and broad-spectrum antiviral drugs are available to treat the SARS-CoV-2-infected patients. Therefore, this review article is planned to gain insight into the mechanism for blocking the entry of SARS-CoV-2, its validation, other inhibition mechanisms, and development of therapeutic drugs and vaccines against SARS-CoV-2.

The Current Recommended Drugs and Strategies for the Treatment of Coronavirus Disease (COVID-19).

BACKGROUND: The coronavirus 2019 (COVID-19) has been known as a pandemic disease by the World Health Organization (WHO) worldwide. The drugs currently used for treatment of COVID-19 are often selected and tested based on their effectiveness in other diseases such as influenza and AIDS and their major identified targets are viral protease, host cell produced protease, viral RNA polymerase, and the interaction site of viral protein with host cell receptors. Until now, there are no approved therapeutic drugs for definitive treatment of this dangerous disease. METHODS: In this article, all of the documentary information, such as clinical trials, original research and reviews, government's database, and treatment guidelines, were reviewed critically and comprehensively. Moreover, it was attempted to present the most common and effective drugs and strategies, to suggest the possible treatment way of COVID19 by focusing on the body's defense mechanism against pathogens. RESULTS: Antiviral drugs and immune-modulatory agents with the traditional medicines using the natural compound are usual accessible treatments. Accordingly, they have better beneficence due to the large existence studies, long time follow-ups, proximity to the natural system, and the normal physiological routine of the pathogen and host interactions. Besides, the serotonergic and dopaminergic pathways are considered as attractive targets to treat human immune, infectious, and cancerous diseases. Fluoxetine, as a host-targeted small molecule with immunomodulatory action, may be known as effective drug for treatment and prevention of COVID19 disease, in combination with antiviral drugs and natural compounds. CONCLUSION: Co-administration of fluoxetine in the treatment of COVID19 could be considered due to the possibility of its interaction with ACE2 receptors, immune-modulatory function, and a proper immune response at the right time. Fluoxetine plays a beneficial role in reducing stress due to fear of infecting by COVID19 or worsening the disease and psychological support for the affected patients.

Overview of therapeutic drug research for COVID-19 in China.

Since the outbreak of novel coronavirus pneumonia (COVID-19) in December 2019, more than 2,500,000 people worldwide have been diagnosed with SARS-CoV-2 as of April 22. In response to this epidemic, China has issued seven trial versions of diagnosis and treatment protocol for COVID-19. According to the information that we have collected so far, this article provides an overview of potential therapeutic drugs and compounds with much attention, including favipiravir and hydroxychloroquine, as well as traditional Chinese medicine, which have been reported with good clinical treatment effects. Moreover, with further understanding of SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise and investigations on these novel anti-SARS-CoV-2 agents are also reviewed.