Therapeutic Options for COVID-19: A Review

Pujari, R; Thommana, Mary V; Mercedes, Brisandi Ruiz; Serwat, Ayna

doi:10.7759/cureus.10480

Cited by 29 publications

(35 citation statements)

References 42 publications

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“…In the absence of a 2019‐nCoV‐specific pharmacological agent, various drugs have been used either singly or combined therapeutic approaches with sporadic success. Many of these drug combinations are being assessed in several of the clinical trials 28 . From among the established antivirals, remdesivir has already progressed to Phase III clinical trials (ClinicalTrials.gov Identifier: NCT04292730) 29 .…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid therapy for 2019‐nCoV‐infected patients: A case series of eight mechanically ventilated patients

AL-Rasheedi¹,

Alhazmi

Almaqwashi

et al. 2021

Clinical Case Reports

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Section: Discussionmentioning

confidence: 99%

Corticosteroid therapy for 2019‐nCoV‐infected patients: A case series of eight mechanically ventilated patients

AL-Rasheedi¹,

Alhazmi

Almaqwashi

et al. 2021

Clinical Case Reports

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“…Stebbing et al used AI-algorithms to identify baricitinib, an approved Janus kinase (JAK)1/JAK2 inhibitor for treating rheumatoid arthritis, to be effective at inhibiting SARS-CoV-2 infection as well as reducing virus induced inflammations ( Stebbing et al, 2020 ). Although baricitinib can cause potential adverse effect including lymphopenia, anemia and increase co-infection crisis with other pathogens ( Pujari et al, 2020 ), its combination with remdesivir is superior to remdesivir alone in improving the clinical recovery rate of patients with COVID-19 with few serious side effects ( Kalil et al, 2021 ). Ge Y. et al (2021) used machine learning and statistical analysis to uncover a ploly-ADP-ribose polymerase (PARP1) inhibitor meguparib (CVL218) which reduced SARS-CoV-2 replication without toxic effects in vitro .…”

Section: Artificial Intelligence-based Drug Discovery For Anti-sars-cov-2mentioning

confidence: 99%

Current Strategies of Antiviral Drug Discovery for COVID-19

Mei

Tan

2021

Front. Mol. Biosci.

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SARS-CoV-2 belongs to the family of enveloped, single-strand RNA viruses known as Betacoronavirus in Coronaviridae, first reported late 2019 in China. It has since been circulating world-wide, causing the COVID-19 epidemic with high infectivity and fatality rates. As of the beginning of April 2021, pandemic SARS-CoV-2 has infected more than 130 million people and led to more than 2.84 million deaths. Given the severity of the epidemic, scientists from academia and industry are rushing to identify antiviral strategies to combat the disease. There are several strategies in antiviral drugs for coronaviruses including empirical testing of known antiviral drugs, large-scale phenotypic screening of compound libraries and target-based drug discovery. To date, an increasing number of drugs have been shown to have anti-coronavirus activities in vitro and in vivo, but only remdesivir and several neutralizing antibodies have been approved by the US FDA for treating COVID-19. However, remdesivir’s clinical effects are controversial and new antiviral drugs are still urgently needed. We will discuss the current status of the drug discovery efforts against COVID-19 and potential future directions. With the ever-increasing movability of human population and globalization of world economy, emerging and reemerging viral infectious diseases seriously threaten public health. Particularly the past and ongoing outbreaks of coronaviruses cause respiratory, enteric, hepatic and neurological diseases in infected animals and human (Woo et al., 2009). The human coronavirus (HCoV) strains (HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1) usually cause common cold with mild, self-limiting upper respiratory tract infections. By contrast, the emergence of three deadly human betacoronaviruses, middle east respiratory syndrome coronavirus (MERS) (Zaki et al., 2012), severe acute respiratory syndrome coronavirus (SARS-CoV) (Lee et al., 2003), the SARS-CoV-2 (Jin et al., 2020a) highlight the need to identify new treatment strategies for viral infections. SARS-CoV-2 is the etiological agent of COVID-19 disease named by World Health Organization (WHO) (Zhu N. et al., 2020). This disease manifests as either an asymptomatic infection or a mild to severe pneumonia. This pandemic disease causes extent morbidity and mortality in the whole world, especially regions out of China. Similar to SARS and MERS, the SARS CoV-2 genome encodes four structural proteins, sixteen non-structural proteins (nsp) and accessory proteins. The structural proteins include spike (S), envelope (E), membrane (M), nucleoprotein (N). The spike glycoprotein directly recognizes and engages cellular receptors during viral entry. The four non-structural proteins including papain-like protease (PLpro), 3-chymotrypsin-like protease (3CLpro), helicase, and RNA-dependent RNA polymerase (RdRp) are key enzymes involved in viral transcription and replication. The spike and the four key enzymes were considered attractive targets to develop antiviral agents (Zumla et al., 2016). The catalytic sites of the four enzymes of SARS-CoV2 share high similarities with SARS CoV and MERS in genomic sequences (Morse et al., 2020). Besides, the structures of the key drug-binding pockets are highly conserved among the three coronaviruses (Morse et al., 2020). Therefore, it follows naturally that existing anti-SARS-CoV and anti-MERS drugs targeting these enzymes can be repurposed for SARS-CoV-2. Based on previous studies in SARS-CoV and MERS-CoV, it is anticipated a number of therapeutics can be used to control or prevent emerging infectious disease COVID-19 (Li and de Clercq, 2020; Wang et al., 2020c; Ita, 2021), these include small-molecule drugs, peptides, and monoclonal antibodies. Given the urgency of the SARS-CoV-2 outbreak, here we discuss the discovery and development of new therapeutics for SARS-CoV-2 infection based on the strategies from which the new drugs are derived.

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“…Treating with systematic corticosteroids was a debate, but the fact that COVID-19 patients can develop a systemic in ammatory response that can lead to lung injury and multisystem organ dysfunction made this class a potential therapeutic option. 8,9 It has been proposed that the potent anti-in ammatory mechanism of corticosteroids might prevent or mitigate these deleterious effects. 10, RECOVERY trial, a multicenter, randomized, open-label trial performed in the United Kingdom, showed that a signi cant mortality reduction at 28-days in hospitalized patients who received dexamethasone for up to 10 days compared to patients who received the standard of care.…”

Section: Introductionmentioning

confidence: 99%

Early Versus Late Use of Dexamethasone in Critically Ill Patients With COVID-19: A Multicenter, Prospective Cohort Study

Sulaiman

Alhubaishi

Juhani

et al. 2021

Preprint

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Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.

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Therapeutic Options for COVID-19: A Review

Cited by 29 publications

References 42 publications

Corticosteroid therapy for 2019‐nCoV‐infected patients: A case series of eight mechanically ventilated patients

Corticosteroid therapy for 2019‐nCoV‐infected patients: A case series of eight mechanically ventilated patients

Current Strategies of Antiviral Drug Discovery for COVID-19

Early Versus Late Use of Dexamethasone in Critically Ill Patients With COVID-19: A Multicenter, Prospective Cohort Study

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