Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern.

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study.

Synergistic Antiviral Activity of Pamapimod and Pioglitazone against SARS-CoV-2 and Its Variants of Concern

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid®and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study.

Acceptance of COVID-19 Vaccine among the Healthcare Workers in the Eastern Cape, South Africa: A Cross Sectional Study.

BACKGROUND: This study assesses the perceptions and acceptance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination. It also examines its influencing factors among the healthcare workers (HCWs) in the Eastern Cape, South Africa. METHODS: In this cross-sectional study performed in November and December 2020, a total of 1308 HCWs from two large academic hospitals participated in the Eastern Cape Healthcare Workers Acquisition of SARS-CoV-2 (ECHAS) study. Validated measures of vaccine hesitancy were explored using a questionnaire. Logistic regression was used to identify the determinants of vaccine hesitancy. RESULTS: The majority were nurses (45.2%), and at risk for unfavourable Covid-19 outcome, due to obesity (62.9%) and having direct contact with individuals confirmed to have Covid-19 (77.1%). The overall acceptance of SARS-CoV-2 vaccine was 90.1%, which differed significantly by level of education. Individuals with lower educational attainment (primary and secondary education) and those with prior vaccine refusal were less likely to accept the SARS-CoV-2 vaccine. However, positive perceptions about the SARS-CoV-2 vaccine were independently associated with vaccine acceptance. CONCLUSIONS: The high level of acceptance of SARS-CoV-2 vaccine is reassuring; however, HCWs with a lower level of education and those with prior vaccine refusal should be targeted for further engagements to address their concerns and fears.