COVID-19 pandemic has spread worldwide at an exponential rate affecting millions of people instantaneously. Currently, various drugs are under investigation to treat an enormously increasing number of COVID-19 patients. This dreadful situation clearly demands an efficient strategy to quickly identify drugs for the successful treatment of COVID-19. Hence, drug repurposing is an effective approach for the rapid discovery of frontline arsenals to fight against COVID-19. Successful application of this approach has resulted in the repurposing of some clinically approved drugs as potential anti-SARS-CoV-2 candidates. Several of these drugs are either antimalarials, antivirals, antibiotics or corticosteroids and they have been repurposed based on their potential to negate virus or reduce lung inflammation. Large numbers of clinical trials have been registered to evaluate the effectiveness and clinical safety of these drugs. Till date, a few clinical studies are complete and the results are primary. WHO also conducted an international, multi-country, open-label, randomized trials-a solidarity trial for four antiviral drugs. However, solidarity trials have few limitations like no placebos were used, additionally any drug may show effectiveness for a particular population in a region which may get neglected in solidarity trial analysis. The ongoing randomized clinical trials can provide reliable long-term follow-up results that will establish both clinical safety and clinical efficacy of these drugs with respect to different regions, populations and may aid up to worldwide COVID-19 treatment research. This review presents a comprehensive update on majorly repurposed drugs namely chloroquine, hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, ribavirin, azithromycin, umifenovir, oseltamivir as well as convalescent plasma therapy used against SARS-CoV-2. The review also summarizes the data recorded on the mechanism of anti-SARS-CoV-2 activity of these repurposed drugs along with the preclinical and clinical findings, therapeutic regimens, pharmacokinetics, and drug-drug interactions.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly pathogenic novel virus that has caused a massive pandemic called coronavirus disease 2019 (COVID-19) worldwide. Wuhan, a city in China became the epicenter of the outbreak of COVID-19 in December 2019. The disease was declared a pandemic globally by the World Health Organization (WHO) on 11 March 2020. SARS-CoV-2 is a beta CoV of the Coronaviridae family which usually causes respiratory symptoms that resemble common cold. Multiple countries have experienced multiple waves of the disease and scientific experts are consistently working to find answers to several unresolved questions, with the aim to find the most suitable ways to contain the virus. Furthermore, potential therapeutic strategies and vaccine development for COVID-19 management are also considered. Currently, substantial efforts have been made to develop successful and safe treatments and SARS-CoV-2 vaccines. Some vaccines, such as inactivated vaccines, nucleic acid-based, and vector-based vaccines, have entered phase 3 clinical trials. Additionally, diverse small molecule drugs, peptides and antibodies are being developed to treat COVID-19. We present here an overview of the virus interaction with the host and environment and anti-CoV therapeutic strategies; including vaccines and other methodologies, designed for prophylaxis and treatment of SARS-CoV-2 infection with the hope that this integrative analysis could help develop novel therapeutic approaches against COVID-19.

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Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host. Besides, the probable routes of virus entry into the nervous system include the hematogenic pathway, through the vagus, the olfactory nerve, or the enteric nervous system. However, the trajectory of SARS-CoV-2 to the brain needs investigation. Furthermore, a Th17-mediated cytokine storm is seen in COVID-19 cases with higher levels of IL-1β/2/7/8/9/ 10/17, GM-CSF, IFN-γ, TNF-α, CXCL-10, MCP1, and MIP1α/β. Some cytokines can cross the blood-brain barrier and activate the brain's immune cells to produce neural cytokines, leading to neuronal dysfunctions. Nonetheless, most of the neurological conditions developed due to viral infections may not have effective and registered treatments. Although, some antivirals may inhibit the virus-mediated pathogenesis and prove to be suitable in COVID-19 treatment. Therefore, clinicians' and researchers' collective expertise may unravel the potential of SARS-CoV-2 infection to prevent short-term and long-term CNS damage.

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