Total infectome characterization of respiratory infections in pre-COVID-19 Wuhan,China

At the end of 2019 Wuhan witnessed an outbreak of “atypical pneumonia” that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their “total infectome”, including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen–Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016–2017.     

Evolutionary dynamics of SARS-CoV-2 circulating in Yogyakarta and Central Java,Indonesia: sequence analysis covering furin cleavage site (FCS) region of the spike protein

International Microbiology - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new virus responsible for the COVID-19 pandemic. The emergence of the new SARS-CoV-2 has been...     

Plant Derived Antiviral Products for Potential Treatment of COVID-19: A Review

COVID-19 caused by SARS-CoV-2 is declared global pandemic. The virus owing high resemblance with SARS-CoV and MERS-CoV has been placed in family of beta-coronavirus. However, transmission and infectivity rate of COVID-19 is quite higher as compared to other members of family. Effective management strategy with potential drug availability will break the virus transmission chain subsequently reduce the pressure on the healthcare system. Extensive research trials are underway to develop novel efficient therapeutics against SARS-CoV-2. In this review, we have discussed the origin and family of coronavirus, structure, genome and pathogenesis of virus SARS-CoV-2 inside human host cell; comparison among SARS, MERS, SARS-CoV-2 and common flu; effective management practices; treatment with immunity boosters; available medication with ongoing clinical trials. We suggest medicinal plants could serve as potential candidates for drug development against COVID-19 infection.     

Knowing and combating the enemy: a brief review on SARS-CoV-2 and computational approaches applied to the discovery of drug candidates

Since the emergence of the new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) at the end of December 2019 in China, and with the urge of the coronavirus disease 2019 (COVID-19) pandemic, there have been huge efforts of many research teams and governmental institutions worldwide to mitigate the current scenario. Reaching more than 1,377,000 deaths in the world and still with a growing number of infections, SARS-CoV-2 remains a critical issue for global health and economic systems, with an urgency for available therapeutic options. In this scenario, as drug repurposing and discovery remains a challenge, computer-aided drug design (CADD) approaches, including machine learning (ML) techniques, can be useful tools to the design and discovery of novel potential antiviral inhibitors against SARS-CoV-2. In this work, we describe and review the current knowledge on this virus and the pandemic, the latest strategies and computational approaches applied to search for treatment options, as well as the challenges to overcome COVID-19.     

Human Organoids as a Promising Platform for Fighting COVID-19

The coronavirus disease 2019 (COVID-19) global pandemic evoked by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a major public health problem with significant morbidity and mortality. Understanding the pathogenesis and molecular mechanisms underlying this novel virus is crucial for both fundamental research and clinical trials in order to devise effective therapies and vaccination regimens. Basic research on SARS-CoV-2 largely depends on ex vivo models that allow viral invasion and replication. Organoid models are now emerging as a valuable tool to investigate viral biology and disease progression, serving as an efficient platform to investigate potential therapies for COVID-19. Here, we summarize various human stem cell-derived organoid types employed in SARS-CoV-2 studies. We highlight key findings from these models, including cell tropisms and molecular mechanisms in viral infection. We also describe their use in identifying potential therapeutic agents against SARS-CoV-2. As more and more advanced organoids emerge, they will facilitate the understanding of disease pathogenesis for drug development in this dreaded pandemic.     

Severe Acute Respiratory Syndrome Coronavirus 2: Manifestations of Disease and Approaches to Treatment and Prevention in Humans

The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus has challenged civilization and modern science in ways that few infectious diseases and natural disasters have previously, causing globally significant human morbidity and mortality and triggering economic downturns across financial markets that will be dealt with for generations. Despite this, the pandemic has also brought an opportunity for humanity to come together and participate in a shared scientific investigation. Clinically, SARS-CoV-2 is associated with lower mortality rates than other recently emerged coronaviruses, such as SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). However, SARS-CoV-2 exhibits efficient human-to-human spread, with transmission often occurring before symptom recognition; this feature averts containment strategies that had worked previously for SARS-CoV and MERS-CoV. Severe COVID-19 disease is characterized by dysregulated inflammatory responses associated with pulmonary congestion and intravascular coagulopathy leading to pneumonia, vascular insults, and multiorgan disease. Approaches to treatment have combined supportive care with antivirals, such as remdesivir, with immunomodulatory medications, including corticosteroids and cytokine-blocking antibody therapies; these treatments have advanced rapidly through clinical trials. Innovative approaches to vaccine development have facilitated rapid advances in design, testing, and distribution. Much remains to be learned about SARS-CoV-2 and COVID-19, and further biomedical research is necessary, including comparative medicine studies in animal models. This overview of COVID-19 in humans will highlight important aspects of disease, relevant pathophysiology, underlying immunology, and therapeutics that have been developed to date.

In December 2019, a cluster of cases of pneumonia without a clear etiology occurred in Wuhan, China. With remarkable speed and efficiency, the etiology of this illness was soon identified as a novel coronavirus; the complete viral genome was sequenced and published on January 10, 2020.¹⁸² These events introduced the world to coronavirus disease 2019 (COVID-19). The disease, now known to be caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into the most significant pandemic of recent times. In less than a year since the virus was first recognized, multiple candidate vaccines were developed worldwide, and some of them rapidly progressed to clinical trials and widespread administration. As the pandemic continues, a number of sequence variants of the virus have emerged around the world. This continued viral evolution highlights the need for continued biomedical research to facilitate understanding of the pathogenesis of COVID-19, seeking innovative therapeutic and preventative strategies for the current and possibly future pandemics. This article will review aspects of SARS-CoV-2 infection of humans and COVID-19, focusing on important aspects of clinical disease, pathophysiology, immunology, and the development of therapeutic and preventative measures to provide context for discussion of the animal models used to study SARS-CoV-2 and COVID-19.     

Interplay between SARS-CoV-2-derived miRNAs,immune system,vitamin D pathway and respiratory system

The new coronavirus pandemic started in China in 2019. The intensity of the disease can range from mild to severe, leading to death in many cases. Despite extensive research in this area, the exact molecular nature of virus is not fully recognized; however, according to pieces of evidence, one of the mechanisms of virus pathogenesis is through the function of viral miRNAs. So, we hypothesized that SARS-CoV-2 pathogenesis may be due to targeting important genes in the host with its miRNAs, which involved in the respiratory system, immune pathways and vitamin D pathways, thus possibly contributing to disease progression and virus survival. Potential miRNA precursors and mature miRNA were predicted and confirmed based on the virus genome. The next step was to predict and identify their target genes and perform functional enrichment analysis to recognize the biological processes connected with these genes in the three pathways mentioned above through several comprehensive databases. Finally, cis-acting regulatory elements in 5′ regulatory regions were analysed, and the analysis of available RNAseq data determined the expression level of genes. We revealed that thirty-nine mature miRNAs could theoretically derive from the SARS-CoV-2 genome. Functional enrichment analysis elucidated three highlighted pathways involved in SARS-CoV-2 pathogenesis: vitamin D, immune system and respiratory system. Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS-CoV-2.     

Manipulation of genes could inhibit SARS-CoV-2 infection that causes COVID-19 pandemics

The year 2020 witnessed an unpredictable pandemic situation due to novel coronavirus (COVID-19) outbreaks. This condition can be more severe if the patient has comorbidities. Failure of viable treatment for such viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is due to lack of identification. Thus, modern and productive biotechnology-based tools are being used to manipulate target genes by introducing the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas (CRISPR-associated) system. Moreover, it has now been used as a tool to inhibit viral replication. Hence, it can be hypothesized that the CRISPR/Cas system can be a viable tool to target both the SARS-CoV-2 genome with specific target RNA sequence and host factors to destroy the SARS-CoV-2 community via inhibition of viral replication and infection. Moreover, comorbidities and COVID-19 escalate the rate of mortality globally, and as a result, we have faced this pandemic. CRISPR/Cas-mediated genetic manipulation to knockdown viral sequences may be a preventive strategy against such pandemic caused by SARS-CoV-2. Furthermore, prophylactic antiviral CRISPR in human cells (PAC-MAN) along with CRISPR/Cas13d efficiently degrades the specific RNA sequence to inhibit viral replication. Therefore, we suggest that CRISPR/Cas system with PAC-MAN could be a useful tool to fight against such a global pandemic caused by SARS-CoV-2. This is an alternative preventive approach of management against the pandemic to destroy the target sequence of RNA in SARS-CoV-2 by viral inhibition.     

干扰素刺激基因与新型冠状病毒相互作用的研究进展

目前新型冠状病毒(severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)感染所致的新型冠状病毒肺炎(corona virus disease, COVID-19)已成为威胁人类健康和安全的全球性流行性疾病。随着新突变株的不断出现,寻找有效治疗药物和靶点迫在眉睫。干扰素刺激基因(interferon-stimulated genes, ISGs)是由干扰素(interferons, IFNs)诱导后表达上调的一类基因,在宿主抵抗病毒感染过程中发挥着至关重要的作用。研究表明,ISGs能够靶向许多病毒复制的不同阶段发挥抗病毒作用,然而SARS-CoV-2也进化出各种策略干扰或逃避宿主天然免疫。因此,全面了解SARS-CoV-2与ISGs相互作用,对于设计抗病毒策略至关重要。本文简要综述不同ISGs抵抗SARS-CoV-2的作用机制,为开发新型的抗病毒药物提供思路和理论依据。     

Structure and Function of N-Terminal Zinc Finger Domain of SARS-CoV-2 NSP2

Virologica Sinica - SARS-CoV-2 has become a global pandemic threatening human health and safety. It is urgent to find effective therapeutic agents and targets with the continuous emergence of novel...     

Targeting ACLY efficiently inhibits SARS-CoV-2 replication

The Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the biggest public health challenge the world has witnessed in the past decades. SARS-CoV-2 undergoes constant mutations and new variants of concerns (VOCs) with altered transmissibility, virulence, and/or susceptibility to vaccines and therapeutics continue to emerge. Detailed analysis of host factors involved in virus replication may help to identify novel treatment targets. In this study, we dissected the metabolome derived from COVID-19 patients to identify key host factors that are required for efficient SARS-CoV-2 replication. Through a series of metabolomic analyses, in vitro, and in vivo investigations, we identified ATP citrate lyase (ACLY) as a novel host factor required for efficient replication of SARS-CoV-2 wild-type and variants, including Omicron. ACLY should be further explored as a novel intervention target for COVID-19.     

Tailored treatment strategies for cancer patients during COVID-19 pandemic

The global pandemic of respiratory disease caused by the novel human coronavirus (SARS-CoV-2) has caused indefinite global distress, uncertainty, and disturbance. This pandemic has had direct and indirect impacts for the healthcare systems across the world, but certain subgroups of patients have been particularly affected. Among these groups are patients with cancer, who as a result of their immunosuppressed status either from the disease itself or as a consequence of treatment, are at increased risk of severe COVID-19 infection and complications. The pandemic has also led to limited resources as medical services have been primarily directed to emergency care. In this context, physicians and healthcare providers have had to balance the importance of continuing treatment of cancer patients with the risk of virus infection.In this review, we outline the treatment strategies for cancer patients during this pandemic, focusing on tailored treatment in this challenging situation of varying risks and benefits.     

Recent biotechnological tools for diagnosis of corona virus disease: A review

Recently, a corona virus disease (COVID-19) caused by a novel corona virus (sevier acute respiratory syndrome corona virus 2; SARS-CoV-2), rapidly spread throughout the world. It has been resulted an unprecedented public health crisis and has become a global threat. WHO declared it as a pandemic due to rapid transmission and severity of the disease. According to WHO, as of 22nd of August 2020, the disease spread over 213 countries of the world having 22,812,491 confirmed cases and 795,132 deaths recorded worldwide. In the absence of suitable antiviral drugs and vaccines, the current pandemic has created an urgent need for accurate diagnostic tools that would be helpful for early detection of the patients. Many tests including classical and high-throughput techniques have developed and obtained U.S. Food and drug administration (FDA) approval. However, efforts are being made to develop new diagnostic tools for detection of the disease. Several molecular diagnostic tests such as real-time-polymerase chain reaction, real-time isothermal loop-mediated amplification (RT-LAMP), full genome analysis by next-generation sequencing, clustered regularly interspaced short palindromic repeats technique and microarray-based assays along with other techniques such as computed tomography scan, biomarkers, biosensor, nanotechnology, serological test, enzyme-linked immunosorbent assay (ELISA), isolation of viral strain in cell culture are currently available for diagnosis of COVID-19 infection. This review provides a brief overview of promising high-throughput techniques currently used for detection of SARS-CoV-2, along with their scope and limitations that may be used for effective control of the disease.     

Open Modification Searching of SARS-CoV-2–Human Protein Interaction Data Reveals Novel Viral Modification Sites

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus 2019 disease, has led to an ongoing global pandemic since 2019. Mass spectrometry can be used to understand the molecular mechanisms of viral infection by SARS-CoV-2, for example, by determining virus–host protein–protein interactions through which SARS-CoV-2 hijacks its human hosts during infection, and to study the role of post-translational modifications. We have reanalyzed public affinity purification–mass spectrometry data using open modification searching to investigate the presence of post-translational modifications in the context of the SARS-CoV-2 virus–host protein–protein interaction network. Based on an over twofold increase in identified spectra, our detected protein interactions show a high overlap with independent mass spectrometry-based SARS-CoV-2 studies and virus–host interactions for alternative viruses, as well as previously unknown protein interactions. In addition, we identified several novel modification sites on SARS-CoV-2 proteins that we investigated in relation to their interactions with host proteins. A detailed analysis of relevant modifications, including phosphorylation, ubiquitination, and S-nitrosylation, provides important hypotheses about the functional role of these modifications during viral infection by SARS-CoV-2.     

Facing the wrath of enigmatic mutations: a review on the emergence of severe acute respiratory syndrome coronavirus 2 variants amid coronavirus disease-19 pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging respiratory virus responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic. More than a year into this pandemic, the COVID-19 fatigue is still escalating and takes hold of the entire world population. Driven by the ongoing geographical expansion and upcoming mutations, the COVID-19 pandemic has taken a new shape in the form of emerging SARS-CoV-2 variants. These mutations in the viral spike (S) protein enhance the virulence of SARS-CoV-2 variants by improving viral infectivity, transmissibility and immune evasion abilities. Such variants have resulted in cluster outbreaks and fresh infection waves in various parts of the world with increased disease severity and poor clinical outcomes. Hence, the variants of SARS-CoV-2 pose a threat to human health and public safety. This review enlists the most recent updates regarding the presently characterized variants of SARS-CoV-2 recognized by the global regulatory health authorities (WHO, CDC). Based on the slender literature on SARS-CoV-2 variants, we collate information on the biological implications of these mutations on virus pathology. We also shed light on the efficacy of therapeutics and COVID-19 vaccines against the emerging SARS-CoV-2 variants.     

Coronavirus and co-infections: A Saudi Arabian perspective

Mortality due to infectious diseases continues to rise globally, despite advances in antimicrobial therapy and supportive care. This is evident with the occurrence of coronavirus disease 2019 (COVID-19) pandemic, instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Saudi Arabia, an eminent country within the Arab region, has had significant impact during global pandemics, concomitant with the fact that millions of Muslims travel to Saudi Arabia for pilgrimages every year. Herein, we discuss the significance of SARS-CoV-1, SARS-CoV-2, as well as the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia with particular reference to global transmission and/or emergence of new variants due to genetic mixing of different strains. Furthermore, we also discuss the role of Saudi Arabia with reference to novel emerging infectious diseases and re-emerging infections, such as Ebola, zika, and monkeypox, as well as in the context on coinfections. Future strategies to limit the spread of viral infections and the pivotal role of Saudi Arabia, are deliberated upon.     

Molecular deconvolution of the neutralizing antibodies induced by an inactivated SARS-CoV-2 virus vaccine

Dear Editor, The rapid emergence and persistence of the pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has had enormous impacts on global health and the economy.Effective vaccines against SARS-CoV-2 are urgently needed to control the coronavirus disease 2019(COVID-19) pandemic,and multiple vaccines have been found to be efficacious in preventing symptomatic COVID-19(Polack et al.,2020;Wu et al.,2020;Jones and Roy,2021).We have developed a traditional beta-propiolactone-inacti-vated aluminum hydroxide-adjuvanted whole-virion SARS-CoV-2 vaccine (BBIBP-CorV),which elicited protective immune responses in clinical trials (Wang et al.,2020;Xia et al.,2021).The vaccine has been granted conditional approvals or emergency use authorizations (EUAs) in China and other countries.     

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and the economy. Considering its clinical impact, with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of SARS-CoV-2. Our limited knowledge of the mechanisms underlying SARS-CoV-2 infection impedes the development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cell (iPSC)-derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and a decreased proportion of specific immune cell types in coronavirus disease 2019 (COVID-19) patients. Replenishing these specific immune cells may serve as useful treatment modality against SARS-CoV-2 infection. Here the authors review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cell types, such as T lymphocytes and natural killer cells, from iPSCs with the aim to aid investigators in making relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cell types to treat COVID-19.     

Construction and applications of SARS-CoV-2 pseudoviruses: a mini review

The ongoing coronavirus disease 2019 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to global public health and social stability. There is an urgent need for understanding the nature and infection mechanism of the virus. Owing to its high infectivity and pathogenicity and lack of effective treatments, live SARS-CoV-2 has to be handled in biosafety level 3 laboratories, which has impeded research into SARS-CoV-2 and the development of vaccines and therapeutics. Pseudotyped viruses that lack certain gene sequences of the virulent virus are safer and can be investigated in biosafety level 2 laboratories, providing a useful virological tool for the study of SARS-CoV-2. In this review, we will discuss the construction of SARS-CoV-2 pseudoviruses based on different packaging systems, current applications, limitations, and further explorations.