Recent insights for the emerging COVID-19:Drug discovery,therapeutic options and vaccine development

SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population,causing over 5.5 million confirmed cases worldwide.As COVID-19 has posed a global threat with significant human casualties and severe economic losses,there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus.Although there are no specific antiviral therapies that have proven effective in randomized clinical trials,currently,the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission.Besides,global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19.Herein,the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.

COVID-19 vaccine candidates and vaccine development platforms available worldwide

The pandemic caused by the worldwide spread of the coronavirus,which first appeared in 2019,has been named coronavirus disease 19(COVID-19).More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),according to the World Health Organization.COVID-19 Dashboard in September 2021.Apart from the wildtype,other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020.Modifications in the SARS-CoV-2 genetic material,such as mutation and recombination,have the ability to modify the viral life span,along with transitivity,cellular tropism,and symptom severity.Several processes are involved in introducing novel vaccines to the population,including vaccine manufacturing,preclinical studies,Food and Drug Administration permission or certification,processing,and marketing.COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies,such as RNA,DNA,protein,and viral vectored vaccines.This comprehensive review,which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality,was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.

Emerging Frontiers in Vaccine Development: A Review of Changing Paradigm

The technology behind vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.

Innovation-driven trend shaping COVID-19 vaccine development in China

Confronted with the Coronavirus disease 2019(COVID-19)pandemic,China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)transmission and mutation,with several innovative platforms,which provides various technical means in this persisting combat.Derived from collaborated researches,vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19.Herein,we outline representative vaccines in multiple routes,while the merits and plights of the existing vaccine strategies are also summarized.Likewise,new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants.All in all,with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease,alongside the traditional routes,the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

Biomaterial-assisted biotherapy:A brief review of biomaterials used in drug delivery,vaccine development,gene therapy,and stem cell therapy

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications,as demonstrated in preclinical and clinical studies.However,the broad applications of biotherapy have been limited by critical challenges,including the lack of safe and efficient de-livery systems and serious side effects.Due to the unique potentials of biomaterials,such as good biocompati-bility and bioactive properties,biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy.The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions,enabling a sustained and localized release of drugs at the target sites.Furthermore,the biomaterials can provide a niche with specific extracellular conditions for the proliferation,differentiation,attachment,and migration of stem cells,leading to tissue regeneration.In this review,the state-of-the-art studies on the applications of bio-materials in biotherapy,including drug delivery,vaccine development,gene therapy,and stem cell therapy,have been summarized.The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

Predicted epitopes of H5N1 bird flu virus by bioinformatics method: a clue for further vaccine development

To the Editor： Bird flu or avian flu, caused by H5N1 virus, is a new emerging infectious disease. It is noted that this H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in many countries. The continued westward dissemination of H5N1 influenza A viruses in avian populations and the nearly 50% mortality of humans infected with H5N1 are a source of great international concern.1 Providing sufficient antiviral drugs and development and approval of new vaccines are the keys for control of the possible emerging pandemic of this atypical influenza.1＇2 Based on the advance in bioinformatics, the immunomics becomes a new alternative in vaccine development.3 Advanced technologies for vaccine development, such as genome sequence analysis, microarray, proteomics approach, high-throughput cloning, bioinformatics database tools and computational vaccinology can be applied for vaccine development of several diseases including new emerging diseases.

The Perspective of Covid-19 Vaccines: What Needs to Be Known and Its Expected Effect on the Human Population?

Background: The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. Purpose: All efforts and strategies are being carried out to contain and reduce the spread of the SARS-CoV-2 virus by tightening the health protocol and using vaccines for the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (Sinovac and Sinopharm from China, Covaxin from Bharat Biotech India) and adjuvanted recombinant protein nanoparticles (Novavax from the USA), which are expected to be able to suppress the spread of the virus and produce a minimum of 70% herd immunity in a population. This study uses a narrative review from reputable publications and is closely related to the topic. Result: Each vaccine’s efficacy varies from the lowest, namely, the Sinovac vaccine (CoronaVac) 50%, to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. However, further rigorous research is still being carried out to develop an effective and efficient vaccine. Health workers are the last bastion to handle COVID-19 patients. Conclusion: The primary purpose of the present immunization is to prevent and minimize the spread of COVID-19. At this time, the availability of a variety of vaccines is expected to provide strategic answers to the pandemic scenario that has afflicted countries all over the world.

Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S.pneumoniae

Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

Control of malaria and other vector-borne protozoan diseases in the tropics: enduring challenges despite considerable progress and achievements

Vector-borne protozoan diseases represent a serious public health challenge,especially in the tropics where poverty together with vector-favorable climates are the aggravating factors.Each of the various strategies currently employed to face these scourges is seriously inadequate.Despite enormous efforts,vaccines-which represent the ideal weapon against these parasitic diseases—are yet to be sufficiently developed and implemented.Chemotherapy and vector control are therefore the sole effective attempts to minimize the disease burden.Nowadays,both strategies are also highly challenged by the phenomenon of drug and insecticide resistance,which affects virtually all interventions currently used.The recently growing support from international organizations and governments of some endemic countries is warmly welcome,and should be optimally exploited in the various approaches to drug and insecticide research and development to overcome the burden of these prevalent diseases,especially malaria,leishmaniasis,Human African Trypanosomiasis(HAT),and Chagas disease.

Recent progress on chikungunya virus research

Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.