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Viruses such as the novel coronavirus, SARS-CoV-2, that is wreaking havoc on the world, depend on interactions of its own proteins with those of the human host cells. Relatively small changes in sequence such as between SARS-CoV and SARS-CoV-2 can dramatically change clinical phenotypes of the virus, including transmission rates and severity of the disease. On the other hand, highly dissimilar virus families such as Coronaviridae, Ebola, and HIV have overlap in functions. In this work we aim to analyze the role of protein sequence in the binding of SARS-CoV-2 virus proteins towards human proteins and compare it to that of the above other viruses. We build supervised machine learning models, using Generalized Additive Models to predict interactions based on sequence features and find that our models perform well with an AUC-PR of 0.65 in a class-skew of 1:10. Analysis of the novel predictions using an independent dataset showed statistically significant enrichment. We further map the importance of specific amino-acid sequence features in predicting binding and summarize what combinations of sequences from the virus and the host is correlated with an interaction. By analyzing the sequence-based embeddings of the interactomes from different viruses and clustering them together we find some functionally similar proteins from different viruses. For example, vif protein from HIV-1, vp24 from Ebola and orf3b from SARS-CoV all function as interferon antagonists. Furthermore, we can differentiate the functions of similar viruses, for example orf3a’s interactions are more diverged than orf7b interactions when comparing SARS-CoV and SARS-CoV-2.

On 30 January 2020, the World Health Organization (WHO) characterized the novel severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) outbreak as a Public Health Emergency of International Concern. Subsequently, on 11 March 2020, WHO declared the global spread of Coronavirus disease 2019 (COVID-19) as a pandemic triggered by this causative virus. This COVID-19 pandemic has impacted lives and livelihoods worldwide, resulting in unprecedented social disruption and economic losses. In order to design and develop effective diagnostics, vaccines and therapeutic interventions against SARS-CoV-2, it is imperative to understand the molecular and cellular mechanisms underpinning the complex interactions between this virus, its variants, and its infected hosts. This chapter provides an overview on the classification, genomic organization and evolution of SARS-CoV-2 (including the emergence of variants from Alpha to Omicron), and summarizes existing and emerging testing strategies. With unprecedented speed, an array of conventional and new COVID-19 vaccines has been developed, evaluated in clinical trials, and administered to billions worldwide. Current and novel antiviral drugs and immunomodulatory approaches are discussed for the therapeutic and prophylactic management of SARS-CoV-2 infections. Finally, much remains for humanity to discover and learn as the world must continue to adapt and live with endemic COVID-19 and SARS-CoV-2 evolution.

The never-ending race for survival between the virus and its host continues to be a major challenge for biologists as well as healthcare professionals. Owing to their simple genome organization, capacity for replication, mutation and adaptation — viruses can evolve rapidly, thereby posing a constant threat to human and other animal hosts. The animal-human species barrier constitutes a considerable hurdle for zoonotic viruses, and often shields humans from the risk of new outbreaks. However, modern lifestyles and advanced technology have diminished geographic barriers, exposing humans to outbreaks initiated in one part of the world, and amplifying the associated health risks and economic losses across the globe. The novel SARS-CoV-2 outbreak that originated from Wuhan, China at the end of 2019 highlights that humans are continuously living under the threat of emerging zoonotic viruses. The Coronavirus disease 2019 (COVID-19) pandemic continues unabated despite the availability and deployment of multiple approved vaccines and supportive therapies. Moreover, SARS-CoV-2 variants have emerged which contain mutations that promote viral transmissibility and/or virulence. Furthermore, these new variants have raised concerns over the protective efficacy of current vaccines and the susceptibility of unvaccinated individuals. This chapter discusses the potential causes and factors that influence viral fitness and host selection leading to the emergence of easily transmissible and highly pathogenic SARS-CoV-2 variants.

Much has been learnt about severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) since the beginning of the Coronavirus disease 2019 (COVID-19) pandemic, including its clinical manifestations, diagnosis, and management. Unlike its zoonotic predecessor SARS-CoV which was largely a symptomatic disease where fever was a hallmark, a significant proportion of SARS-CoV-2 infections can be asymptomatic (40%), while severe disease (requiring oxygen supplementation or ventilatory support) occurs in approximately 20%, and mortality in about 2% of infected patients. Extra-pulmonary COVID-19 manifestations are also more protean, compared to SARS. Supportive care is the mainstay of treatment for most patients, but for those who progress to severe COVID-19, antivirals such as remdesivir and immunomodulatory treatment (such as corticosteroids or the JAK-inhibitor, baricitinib) may improve outcomes. While further advances in the management of COVID-19 are anticipated (including novel therapies), prevention of infection through public health measures (including vaccination), will remain as vital facets in confronting this pandemic.

Detection and diagnosis platforms play key roles in early warning, outbreak control and exit strategy for any pandemic, and they are especially pertinent for the Coronavirus disease 2019 (COVID-19) pandemic. The challenges posed by the speed and extent of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) spread around the globe also offered unprecedented opportunities for the development and deployment of novel strategies and products — not only vaccines and therapeutics, but also diagnostics. This chapter provides a brief summary of the vast array of molecular, serological, cell-based and other diagnostic tools for the specific detection of SARS-CoV-2 infections and immune responses. The focus is on the principles and applications of each platform, while detailed protocols can be found in the cited references.

One fundamental question about any novel pathogen is: how does it transmit? Answering this question will help to protect ourselves from the agent, at least until effective vaccines and antiviral therapies can be developed, especially if it is an agent of moderate to high lethality. Initially, at the start of the Coronavirus disease 2019 (COVID-19) pandemic, more emphasis was placed on handwashing rather than on droplet and aerosol transmission. Although severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2)-infected secretions such as saliva can spread the virus to hands, it became increasing evident that the virus mostly transmitted through close contact (though not necessarily touching), whilst people were breathing, talking, laughing, singing, coughing and sneezing near one another. During such respiratory activities, droplets and aerosols are produced together, and the amount of transmission due to these different-sized liquid particles will likely vary between individuals at different stages of their infection and illness. This question became even more complex as it emerged that viral transmission can occur for several days before symptom onset, and that asymptomatic cases can also shed just as much virus and potentially transmit it just as well as symptomatic cases. This chapter summarizes our understanding of how SARS-CoV-2 transmits and the infection control precautions to reduce this.

The replication cycle of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) shares many features with other human Coronaviruses such as SARS-CoV and Middle East respiratory syndrome Coronavirus (MERS-CoV). Recent studies have elucidated the viral strategies of antagonizing the host immune response, including a multitude of mechanisms by which SARS-CoV-2 can dampen the interferon-mediated innate immunity. Furthermore, an imbalance and delay in interferon production, and exaggerated secretion of pro-inflammatory cytokines contribute to the severe immunopathology of Coronavirus disease 2019 (COVID-19). This chapter summarizes our current understanding of the intimate relationship between SARS-CoV-2 and the host innate and adaptive immune responses. The strategies that the virus utilizes to exploit cellular resources and to evade the innate immune system are described. The chapter provides a detailed discussion of interferon-mediated innate immunity, interferon evasion and antagonism by SARS-CoV-2 and human Coronaviruses.

The emergence of the novel severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) Coronavirus resulted in a global pandemic due to its nature of rapid transmission and variable severities that facilitated its spread worldwide. Correspondingly, owing to advances in molecular technologies, information on this virus is generated at an unprecedented pace. Since the onset of the pandemic, multiple high-throughput “omics” analyses — including transcriptomics and proteomics of different viral infection models — have been made readily available to the research and wider community. The availability and ability to rapidly generate these data facilitate the deciphering of virus–host interactions during SARS-CoV-2 infection — thus enhancing understanding of the viral transmission, host susceptibility, pathogenesis, viral evolution, and disease complications. Such information is vital for eventual applications towards biomarker and treatment discovery against Coronavirus disease 2019 (COVID-19), and can serve as useful models for future pandemic responses.

The current pandemic SARS-CoV-2 (also known as 2019-nCoV and COVID-19) viral infection is growing globally and has created a disastrous situation all over the world. One of the biggest challenges is that no drugs are available to treat this life-threatening disease. As no drugs are available for definitive treatment of this disease and the mortality rate is very high, there is an utmost need to cure the infection using novel technologies. This study will point out some new antimicrobial technologies that have great potentials for eradicating and preventing emerging infections. They can be considered as treatments of choice for viral infections in the future.

Emerging pathogens have no known therapies or vaccines and therefore can only be controlled via traditional methods of contact tracing, quarantine and isolation that require rapid and widespread testing. The most recent outbreak from an emerging pathogen is due to the highly transmissible SARS-CoV-2 virus causing COVID-19 disease, which is associated with no symptoms or mild symptoms in 80–90% of the infected individuals, while in the remainder of the patients it exhibits severe illness that can be lethal or persist for several weeks to months after infection. The first tests to diagnose infection by SARS-CoV-2 were developed soon after the genome of the virus became known, and use probes to measure viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These tests are highly sensitive and specific but can require several days to return results, which makes contact tracing and more generally efforts to control the spread of the infection very difficult. Furthermore, the sensitivity threshold is orders of magnitude below the viral load necessary for transmission; therefore, individuals recovering from the infection may still be have a positive test and be required to isolate unnecessarily while they are no longer infectious. Antigen tests were subsequently developed that use antibodies mostly targeted to the nucleocapsid protein of the virus. These tests are about 100 times less sensitive than RT-PCR, yes they detect viral loads that are about 1/10 that needed for transmission. Furthermore, such tests are potentially much cheaper than RT-PCR and yield results in 15 min or less. Antibody, also known as serological testing, is available and can provide useful information to understand the extent to which a population has been exposed to the virus; however, it is not a good indicator of current infection and not useful for infection control. Viral transmission models that incorporate testing and contact tracing show that infection control is much more readily achieved by increasing testing frequency than by using higher sensitivity testing. For example, compared to no testing at all, testing once every other week has a marginal benefit, while testing weekly can decrease the number of infections to 20–40%, and testing twice weekly or more can bring about a 95%þ reduction in infections. These lessons learned from dealing from the COVID-19 pandemic should guide future planning against potential emerging viruses.