Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

Abstract

The rapid development of vaccines to combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has been critical to reduce the severity of COVID-19. However, the continuous emergence of new SARS-CoV-2 subtypes highlights the need to develop additional approaches that oppose viral infections. Targeting host factors that support virus entry, replication, and propagation provide opportunities to lower SARS-CoV-2 infection rates and improve COVID-19 outcome. This includes cellular cholesterol, which is critical for viral spike proteins to capture the host machinery for SARS-CoV-2 cell entry. Once endocytosed, exit of SARS-CoV-2 from the late endosomal/lysosomal compartment occurs in a cholesterol-sensitive manner. In addition, effective release of new viral particles also requires cholesterol. Hence, cholesterol-lowering statins, proprotein convertase subtilisin/kexin type 9 antibodies, and ezetimibe have revealed potential to protect against COVID-19. In addition, pharmacological inhibition of cholesterol exiting late endosomes/lysosomes identified drug candidates, including antifungals, to block SARS-CoV-2 infection. This review describes the multiple roles of cholesterol at the cell surface and endolysosomes for SARS-CoV-2 entry and the potential of drugs targeting cholesterol homeostasis to reduce SARS-CoV-2 infectivity and COVID-19 disease severity.

Serum Adiponectin Predicts COVID-19 Severity

“…Common medications, such as statins and metformin, of our cohorts were not documented. Statins have been described to protect against SARS-CoV-2 infection and adverse disease outcomes [65][66][67], and have also been found to induce adiponectin levels [9]. Metformin appears to protect against severe COVID-19 [68] and elevated serum adiponectin levels in several patient cohorts [69].…”

Proprotein Convertase Subtilisin/Kexin Type 9 Induction in COVID-19 Is Poorly Associated with Disease Severity and Cholesterol Levels

“…Low levels of PCSK9 may be related to higher ACE2 activity, which exerts anti-inflammatory activities. However, whether PCSK9 antibodies prevent PCSK9-induced degradation of ACE2 needs further study [ 32 , 42 ].…”

Therapeutic combination of "keys" to target low-density lipoprotein cholesterol level

“…Эзетимиб также подтвердил свою безопасность у пациентов с подтвержденным диагнозом COVID-19 [19,20], а в израильском когортном исследовании прием данного препарата даже ассоциировался со снижением риска госпитализации по поводу COVID-19 и его осложнений [21].…”

“…MEDITSINSKIY SOVET 2024;18 (5): [16][17][18][19][20][21] Cardiology ВВЕДЕНИЕ Более 50% пациентов в России, согласно исследованию «Эпидемиология сердечно-сосудистых заболеваний (CCЗ)» (ЭССЕ-РФ), имеют гиперхолестеринемию, 20,6%выраженное повышение холестерина липопротеинов низкой плотности (ХС-ЛПНП) (более 4,3 ммоль/л) [1]. ХС-ЛПНП -класс липопротеинов крови, являющийся наиболее атерогенным, это не просто биомаркеры повышенного риска, но и причинный фактор в патофизиологии атеросклеротических ССЗ, требующий медикаментозной коррекции [2].…”